key: cord-0006591-4o8uu6d5 authors: Kivity, Shaye; Katz, Uriel; Daniel, Natalie; Nussinovitch, Udi; Papageorgiou, Neophytos; Shoenfeld, Yehuda title: Evidence for the Use of Intravenous Immunoglobulins—A Review of the Literature date: 2009-07-10 journal: Clin Rev Allergy Immunol DOI: 10.1007/s12016-009-8155-9 sha: 9b71a937bc54eed0edc41cb938793004ea8bf8b8 doc_id: 6591 cord_uid: 4o8uu6d5 Intravenous immunoglobulins (IVIg) were first introduced in the middle of the twentieth century for the treatment of primary immunodeficiencies. In 1981, Paul Imbach noticed an improvement of immune-mediated thrombocytopenia, in patients receiving IVIg for immunodeficiencies. This opened a new era for the treatment of autoimmune conditions with IVIg. Since then, IVIg has become an important treatment option in a wide spectrum of diseases, including autoimmune and acute inflammatory conditions, most of them off-label (not included in the US Food and Drug Administration recommendation). A panel of immunologists and internists with experience in IVIg therapy reviewed the medical literature for published data concerning treatment with IVIg. The quality of evidence was assessed, and a summary of the available relevant literature in each disease was given. To our knowledge, this is the first all-inclusive comprehensive review, developed to assist the clinician when considering the use of IVIg in autoimmune diseases, immune deficiencies, and other conditions. Abstract Intravenous immunoglobulins (IVIg) were first introduced in the middle of the twentieth century for the treatment of primary immunodeficiencies. In 1981, Paul Imbach noticed an improvement of immune-mediated thrombocytopenia, in patients receiving IVIg for immunodeficiencies. This opened a new era for the treatment of autoimmune conditions with IVIg. Since then, IVIg has become an important treatment option in a wide spectrum of diseases, including autoimmune and acute inflammatory conditions, most of them off-label (not included in the US Food and Drug Administration recommendation). A panel of immunologists and internists with experience in IVIg therapy reviewed the medical literature for published data concerning treatment with IVIg. The quality of evidence was assessed, and a summary of the available relevant literature in each disease was given. To our knowledge, this is the first all-inclusive comprehensive review, developed to assist the clinician when considering the use of IVIg in autoimmune diseases, immune deficiencies, and other conditions. Intravenous immunoglobulins (IVIg) are gamma globulins purified from the pooled plasma of thousands of donors, typically containing more than 95% of unmodified immunoglobulin G (IgG) and only trace amounts of IgA or IgM. Immune globulin products from human plasma were first used in 1952 to treat immune deficiencies. About 30 years later, Paul Imbach observed that patients with immune thrombocytopenia and agammaglobulinemia receiving immunoglobulins as immune replacement therapy recovered from their thrombocytopenia [1] . This was the first observation to suggest treatment of autoimmune diseases with IVIg. Later on, the ability to administer large quantities of immunoglobulin intravenously was gained owing to technological advances, among them the improvement in plasma fractionation. As a result, IVIg slowly became an important treatment option in a number of diseases beyond primary immune deficiencies, including autoimmune and acute inflammatory conditions, most of them off-label indications. These indications have crossed over into almost every medical specialty. The US Food and Drug Administration (FDA) has approved the use of IVIg for the following six conditions: primary immunodeficiencies, immune thrombocytopenic purpura (ITP), Kawasaki disease, hematopoietic stem cell transplantation, chronic B cell lymphocytic leukemia, and pediatric HIV. Many offlabel indications have emerged; some of these new indications for IVIg are based on solid clinical evidence; others are based on relatively few data or anecdotal reports (case series, case reports). This lack of firm evidence is due to the difficulty in performing appropriate clinical trials in diseases with low prevalence. There is a need for an evidence-based guidance for the use of IVIg to help improve patient care consistency. Another issue is the efficacy of different preparations of IVIg. The FDA has recommended the use of particular preparations of IVIg for each labeled indication in accordance to the specific preparation used to demonstrate a beneficial effect. Of course, there is selection bias since generally only a few preparations have been tested for a given disease. This is in recognition of the difficulty to reproduce the properties of an IVIg preparation, which may vary from one manufacturer to the other due to differences in the donor population, number of donors, period of donation, production methods, virus/bacteria inactivation methods, etc. IVIg properties may also vary from batch to batch made by the same manufacturer, complicating homogeneity even more. Possible mechanisms of action of IVIg in autoimmune and inflammatory diseases are: intact Fc-dependent blockage of IgG (as in ITP), inhibition of membrane attack complexes (C5b-C9) and activated components C3b and C4b (as in Kawasaki's disease), and anti-idiotypes against autoantibodies (as in acquired hemophilia due to autoantibodies against factor VIII). IVIg also contains various cytokines and natural antibodies that may act against pathogens, altered molecules, cells, autoreactive B cell clones, and tumors. IVIg therapy reviewed the medical literature indexed in PubMed using specific terms for each specific disease/ condition AND ("IVIg" OR "IgIV" OR "Intravenous Immunoglobuli*" OR "gamma globuli*"). There was no limitation on language, year of publication, or publication status. We used all clinical data ranging from multicentered randomized controlled trials (RCT) and meta-analysis to case reports. From each article, we extracted details of the study design, number of patients, type of intervention including the dose and IVIg preparation used (if mentioned), and response to treatment. The relevant data were summarized in a hierarchical manner according to the study design and number of participants. When evidence was based on higher level of evidence studies, such as RCTs, lower levels of evidence studies (such as case control studies) were disregarded. Specific diseases were classified in tables according to the specialty they belong to and are followed by a short summary of recommendations, including the level of evidence and the strength of recommendation, as assessed by known guidelines (Table 1 ) [2] . To our knowledge, this is the first comprehensive review which summarizes all up-to-date published data regarding the usage of IVIg in autoimmune diseases, immune deficiencies, and other indications. The tables below summarize the clinical data gathered from studies dealing with IVIg treatment for different conditions. Each table is followed by our evidence-based recommendations for the usage of IVIg. The following conditions refer to ( Table 2) . Level of evidence B Systemic lupus erythematosus (SLE) is a multisystemic disease with various manifestations. There is some evidence that IVIg, given in patients without an increased risk for thromboembolic events or renal failure, is a safe and beneficial adjunct therapy for SLE patients with systemic flare-ups who are resistant to or refuse conventional treatment (strength of recommendation IIa). Level of evidence C Lupus myocarditis is an uncommon but severe complication of SLE. There is no consensus on the specific treatment of SLE myocarditis. Most reports describe treatment with high-dose corticosteroids (CS), followed by either cyclophosphamide or azathioprine, in addition to conventional treatment for heart failure. There is little evidence that IVIg is effective when immunosuppressive therapy fails (strength of recommendation IIa). Level of evidence B As with the treatment of ITP, IVIg seems to be useful in managing the bleeding complications of patients with lupus-associated thrombocytopenia (strength of recommendation I). Level of evidence C Standard therapy for subacute cutaneous lupus erythematosus (SCLE) includes CS (topical, intralesional, systemic), antimalarials, and other immunosuppressive agents. IVIg may be considered in refractory cases, but more study should be done (strength of recommendation IIa). Level of evidence C Kikuchi, also called histiocytic necrotizing lymphadenitis, is a rare benign disease. There is little evidence that treatment with IVIg is superior to other antiinflammatory treatments (strength of recommendation IIa). Level of recommendation C Giving the fact that adult still disease responds to CS and biological and anti-tumor necrosis factor (TNF) treatment, there is low-level evidence that IVIg has an additional benefit for treatment of this disease (strength of recommendation IIa). Level of recommendation B Immunosuppression with CSs and cytotoxic agents should be used in systemic vasculitis before considering IVIg. There is however some evidence that IVIg might be useful and therefore in refractory cases it may be worth to try (strength of recommendation IIa). Level of evidence B CSS is a rare disease. The initial management of CSS consists of high doses of CS. For patients with severe disease or those who are unresponsive to CS, treatment with IVIg was warranted (strength of recommendation IIa). Level of evidence B Infection with hepatitis C virus (HCV) may be associated with a variety of autoimmune phenomena causing a therapeutic dilemma for treatment with interferon alpha (IFN alpha), which stimulates autoimmune symptoms, or with CS, which may lead to an increase of viral load. Treatment with IVIg may act synergistically with Table 1 Recommendation guidelines [2] Level of evidence A: more than one randomized controlled trial (RCT)/meta-analysis B: a single RCT or well-designed nonrandomized trial like prospective observational registries (case-controls, cohorts). C: expert consensus: this includes case reports and retrospective series; here, the expert decides based on his experience Strength of recommendation Class I: conditions for which there is evidence and/or general agreement that a given procedure/therapy is useful and effective Class II: conditions for which there is conflicting evidence and/or divergence of opinion about the usefulness/efficacy of performing the procedure/therapy Class IIa: weight of evidence/opinion is in favor of usefulness/efficacy Class IIb: usefulness/efficacy is less well established by evidence/opinion Class III: conditions for which there is evidence and/or general agreement that a procedure/therapy is not useful/effective and in some cases may be harmful (2) , acquired factor VIII inhibitors (2) , acquired von Willebrand disease (2) , pure red cell aplasia(3), pancytopenia (1), myelofibrosis (1), pneumonitis (2) , pleural effusion (1), pericarditis (2) , myocarditis (2) , CNS Improvement of SLE-related condition Level of evidence C Mixed connective tissue disease (MCTD) is an autoimmune condition which combines features of polymyositis, systemic lupus erythematosus, scleroderma, and dermatomyositis and is thus considered an overlap syndrome. There is scarce evidence that treatment with IVIg helps to improve skin manifestations in MCTD (strength of recommendation IIa). Level of evidence B Systemic sclerosis is characterized by hardening and scarring of the skin and inner organs. There is some evidence that treatment with IVIg helps to improve skin and systemic symptoms (strength of recommendation I). Level of evidence A There is evidence that IVIg is useful for the treatment of patients with severe chronic JRA; its treatment may help also reduce the need for CS and other immunosuppressive therapy (strength of recommendation I). Level of evidence B There is hardly any convincing evidence that IVIg benefits patients with RA (strength of recommendation IIb). Level of evidence C There is some evidence that patients with ataxic sensory neuropathy refractory to immunosuppressive therapy will benefit from IVIg (strength of recommendation IIa). Level of evidence B In patients with DM and PM that are resistant or partially responsive to conventional therapies, IVIg was effective (strength of recommendation I). Level of evidence A In IBM, IVIg showed marginal improvements in muscle strength which were nonsignificant and thus were not recommended (strength of recommendation III). Level of evidence C Behcet's disease is a multisystemic disorder presenting with recurrent oral and genital ulcers as well as ocular and central nervous system involvement. The severe cases may respond to systemic CSs, interferon, or anti-TNF therapy. There is some evidence to support IVIg treatment for refractory eye and skin involvement (strength of recommendation I). The following conditions refer to (Table 3) . Level of evidence B There is weak evidence that IVIg is useful in the treatment of acquired hemophilia. IVIg may be tried in the case in which CS and cytotoxic agents fail or when facing an emergency situation as an additional therapy IVIg (strength of recommendation IIa). Level of evidence A There is strong evidence that IVIg is of benefit in reducing the number and severity of infections in patients with acquired hypogammaglobulinemia in the context of hematological malignancy (strength of recom-mendation I). While this is true, both cost and the potential of adverse effects, most prominently acute renal failure and thromboembolic phenomena [3] [4] [5] , prevent a clear-cut recommendation for the use of IVIg in acquired hypogammaglobulinemia. With this in mind, IVIg may be recommended at the replacement dose of 400 mg/kg each 3 to 4 weeks in cases in which severe or recurrent infections have occurred. Level of evidence C Pure red cell aplasia may be immunemediated due to a background neoplasia, most frequently hematologic, or due to an immune disease or as an immune response triggered by drugs. It may also occur secondary to parvovirus B19 infection which may also lead to aplastic anemia. Treatment of the causative disease is the most important issue. Weak evidence supports the use of IVIg in pure red cell aplasia. IVIg may however be used in the case in which first-line therapy (i.e., CS and immunosuppressive drugs) fails to achieve a remission (strength of recommendation IIa). IVIg is first-line therapy in immunosuppressed hosts in which infection with parvovirus B19 results in pure red cell aplasia. Level of evidence B and C According to Federici and colleagues [6] , 48% of the cases of acquired von Willebrand syndrome are associated with lymphoproliferative diseases, 15% with myeloproliferative disorders, and 21% with cardiovascular diseases. In another paper, Federici and colleagues [7] claim that 33% of the reported cases are associated with a monoclonal gammopathy of uncertain significance. Then, the detection and specific treatment of the underlying disease is as important as the immediate therapy of the coagulation disorder. In accordance to the scant existing evidence of IVIg therapy in this disorder, IVIg should be used in cases of standard therapy (desmopressin and factor VIII/von Willebrand factor concentrate) failure and in urgent situations as an addition to such therapy (strength of recommendation IIb). IVIg may also be used in the preparation for surgery. Level of evidence C While idiopathic aplastic anemia can be transient as in the case of parvovirus-B19-induced bone marrow depression, idiopathic aplastic anemia should first be treated with immunosuppressive drugs like CS or cyclosporine or with antithymocyte or antilymphocyte immunoglobulins as well as supportive blood components transfusions. Stem cell POEMS syndrome polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes transplantation is always the alternative in the case of failure of the aforementioned treatments. Due to the low level of evidence of IVIg for the treatment of idiopathic aplastic anemia, we cannot recommend its liberal use but it may be tried in the case of treatment failure, before stem cell transplantation is performed (strength of recommendation IIb). Level of evidence B Immunosuppression with CS and then cytotoxic agents should be used in autoimmune hemolytic anemia before considering IVIg. There is however some evidence that IVIg might be useful and therefore in refractory cases before considering splenectomy it may be worth a try (strength of recommendation IIb). Level of evidence C Although immune neutropenia may also be an adverse effect resulting from IVIg treatment as have been published elsewhere [8] , IVIg has been used to treat immune neutropenia. The evidence is weak and responses are not as good as those with CS and granulocyte colony-stimulating factor (strength of recommendation IIb). Level of evidence C Evans' syndrome is usually a therapyresistant condition that has been treated combining CS, IVIg, and immunosuppressive therapy. Although convincing evidence is lacking for the use of IVIg in view of the severity and the refractory nature of several cases of Evans' syndrome, IVIg may be considered among the treatment options generally together with CS with or without immunosuppressive therapy (strength of recommendation IIb). Level of evidence B The only study comparing IVIg against other treatment (CS), although nonrandomized, suggests that IVIg raises the platelet number and prevents intracranial bleeding in a significant percentage of treated patients. The level of evidence is low, but the alternatives for prenatal treatment of fetuses at risk are not better and the risks involved are huge (strength of recommendation IIb). Level of evidence A Strong evidence denies any benefit from the use of IVIg around stem cell/bone marrow transplantation, both from the infectious or from the graftversus-host disease point of views (strength of recommendation III). Level of evidence A There is clear evidence for the use of IVIg when facing newborn hemolysis as it reduces the need of plasmapheresis (PP) therapy (strength of recommendation I). Level of evidence C There is no reliable evidence to recommend the use of IVIg to prevent or to treat hemolytic transfusion reactions (strength of evidence IIb). Level of evidence C Apart from two papers reporting two cases and another case, there is no evidence to recommend the use of IVIg either to prevent or to treat hemolytic transfusion reactions in sickle cell patients, specially taking into consideration the additional risk of thrombosis due to a change in the rheologic properties of the blood after IVIg infusion (strength of recommendation IIb). Level of evidence B There is conflicting evidence that IVIg benefits patients with hemolytic uremic syndrome (strength of recommendation IIb). Level of evidence B There is no evidence that IVIg benefits patients with thrombotic thrombocytopenic purpura (strength of recommendation III). Level of evidence C There is low-level evidence that IVIg is useful for this disease. On the other hand, thromboembolic phenomena, which are part of the heparin-induced thrombocytopenia clinical picture, might be enhanced by the rheologic blood changes after IVIg infusion. Therefore, IVIg should not be generally recommended for this disease (strength of recommendation IIb). Level of evidence B Evidence comes only from one crossover randomized placebo-controlled trial which supports the use of IVIg in HIV-associated thrombocytopenia, especially when platelet count is very low or the risk of bleeding is high (strength of recommendation IIa). Level of evidence A Since Imbach's observation [1] , acute ITP has been the prototype of IVIg-responsive immune disease. There is consistent evidence that IVIg is beneficial in children with ITP (strength of recommendation I). Notwithstanding this, CS therapy is still the first-line treatment for ITP, and single-dose anti-D immunoglobulin [9, 10] is a [8] good alternative for Rh-positive patients. IVIg should be considered when there is bleeding or when the bleeding risk is high or upon failure of other treatments. In adult acute ITP patients, there is no placebo-controlled RCT, but when compared with CS IVIg induces a faster response. Again, CS is the first-line treatment for adults but IVIg may be given in severe or refractory cases. There is weak evidence that IVIg can improve mother and fetal prognosis in pregnancy. IVIg may be used when a fast correction in platelet number is needed. Level of evidence B By the merits of its own research, IVIg may be considered to treat ITP in the context of HIV. Although no hard evidence exists due to the fact that this particular group of patients has not been investigated as well as has non-HIV-related ITP, it will be hard to argue that the recommendation of the latter may not be extended to HIV-related ITP (strength of recommendation I). In chronic ITP, IVIg has so far not demonstrated a plausible benefit. Only prospective noncontrolled trials are available and we found only one evaluating maintenance IVIg for chronic ITP, in which the overwhelming majority of patients had a recrudescence of thrombocytopenia in spite of a good initial response to IVIg (level of evidence and strength of recommendation B-IIb). A small number of patients benefited and therefore IVIg might be tried in drug refractory cases of chronic ITP in which there is a contraindication for splenectomy. Level of evidence C Series of patients treated with fast response to IVIg suggest a benefit of IVIg treatment in posttransfusional purpura, although with low-level of evidence. In the context of a patient with severe risk to bleeding or actual bleeding, IVIg can be used if the diagnosis of posttransfusional purpura is made (strength of recommendation IIb). Level of evidence C Hemophagocytic syndrome is a severe reaction leading to high mortality. Inconsistent and low-level evidence do not warrant a clear-cut recommendation of IVIg for this syndrome. However, due to the lack of effective and standardized treatment in an otherwise highly lethal disease, IVIg may be used along with other therapies like monoclonal antibodies, CS, cytotoxic drugs, and support measures (strength of recommendation IIb). Level of evidence C There are only anecdotal reports, both showing benefit and lack of benefit. There is no evidence that IVIg has a beneficial effect on polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (strength of recommendation IIb). Level of evidence C There is no convincing evidence that IVIg has any beneficial effect in this disease (strength of recommendation IIb). The following conditions refer to (Table 4 ). Level of evidence B IVIg is not used for the treatment of CMV infection but may be helpful in treatment of hemophagocytic syndrome related to CMV and other viruses (see hematology section); there is some evidence for its effectiveness in preventing seroconversion in transplant patients who are immunosuppressed (strength of recommendation IIa). Level of evidence B IVIg can reduce infections in children with perinatal HIV but has not been proven to reduce mortality (strength of recommendation IIa). Level of evidence B No evidence for the effectiveness of IVIg in the treatment in malaria exists (strength recommendation III). Level of evidence A Postpolio syndrome (PPS) typically affects survivors of poliovirus infection, 15-20 years after the original infection, with fatigue, muscular weakness, and pain. There are two RCTs demonstrating some inconsistent evidence for the effectiveness of IVIg treatment on quality of life, pain, and muscle strength in patients with PPS (strength of recommendation IIa). Level of evidence A Sepsis is a life-threatening condition, resulting mainly from the patient's immune response to a severe infection. Significant but heterogenic reduction in mortality with IVIg treatment in septic patients was demonstrated in a meta-analysis of 14 RCTs. These results were not confirmed when only high-quality studies were analyzed (strength of recommendation IIa). Level of evidence C Infection with West Nile virus can cause fatal encephalitis in immunosuppressed and elderly patients, in which case effective treatment is lacking. The effectiveness of IVIg in these situations is supported by a few case reports and may be considered (strength of recommendation IIa) Level of evidence A Treatment with IVIg has not proven to reduce infectious-related mortality in postsurgical patients, but there is inconsistent evidence that IVIg reduces ICUrelated infections and hospital stay in these patients (strength of recommendation IIa). Level of evidence A There is conflicting evidence regarding the usefulness of IVIg treatment for these patients. It should be taken into consideration that patients treated with IVIg after bone marrow transplantation (BMT) may have a higher incidence of fatal hepatic veno-occlusive disease (strength of recommendation IIa). Level of evidence B Necrotizing fasciitis is caused by deep-skin infection with bacteria, mainly group A streptococcus. The mainstay of nuclear factor treatment is prompt surgical exploration and antibiotic therapy. IVIg might have additional benefit to antibiotic therapy for treatment of patients who refuse surgery or are not surgical candidates. (strength of recommendation IIa). Level of evidence B There is weak evidence that IVIg is useful in the treatment of recurrent otitis media (strength of recommendation IIb). Level of evidence B Some evidence that IVIg is effective in preventing perinatal transmission of varicella. IVIg may also be used for treatment adults with severe respiratory failure due to varicella pneumonia (level of recommendation IIa). The following conditions refer to (Table 5) . Level of evidence B Although the best level of evidence is not strong, the improvement shown for treated pregnancies is beyond the natural possibility of a subsequent spared pregnancy which has been estimated to be approximately 40% ( [11] #110). In view of this data and the difficulty for large RCTs, IVIg may be considered to prevent recurrent perinatal hemochromatosis (strength of recommendation IIa). Level of evidence A There is evidence that IVIg improves the outcome of pregnancy in secondary recurrent miscarriage (in women that had a previous pregnancy that reached at least the second trimester (strength of recommendation IIb)). This has so far not been shown for primary recurrent miscarriage (strength of recommendation III). Level of evidence A The evidence is against the use of IVIg in pregnancy of women affected by antiphospholipid syndrome (strength of recommendation III). Level of evidence B Evidence from a small RCT indicates that IVIg may reduce the rate of fetal infection after premature rupture of membranes (strength of recommendation IIa). Level of evidence A The evidence is scarce but the only meta-analysis based on data from three RCTs found a benefit in the number of live births in women treated with IVIg. After in vitro fertilization (IVF) failure, IVIg along with IVF techniques may be weighted (strength of recommendation IIb). The following conditions refer to (Table 6) . Level of evidence B A randomized double-blind study has demonstrated significant increase of ejection fraction (EF) and improved quality of life following IVIg administration, regardless of the congestive heart failure (CHF) cause. CHF is a proinflammatory state due to an increase of cytokines such as TNF-α and interleukin (IL)-1. Some of the cytokines have been shown to induce myocardial dysfunction due to negative inotropic effect [12] . Another possible mechanism in CHF pathogenesis is mediated by anti-β1 adrenergic receptor (strength of recommendation IIa). Level of evidence B Dilated cardiomyopathy (DCM) is caused by various triggers or may be idiopathic. Immune abnormalities and autoantibodies may play a role in the pathogenesis. Nevertheless, no significant effect was noted following IVIg administration in recent-onset DCM compared to placebo [13] . A trial on 17 patients with idiopathic DCM showed significant improvement of EF and quality of life compared with placebo [14] . Therefore, IVIg treatment in DCM remains controversial, and it is possible that IVIg treatment is beneficial in specific subpopulation and when treatment is initiated at a certain time window (strength of recommendation IIb). Level of evidence C Peripartum cardiomyopathy (PPCM) is a rare disorder. It is believed that autoimmune mechanisms play a role in the pathogenesis. In a small nonrandomized retrospective trial, there was a significant improvement of EF following IVIg administration compared with conventional treatment. Although there is partial evidence of IVIg effectiveness in PPCM, its use should be considered due to the generally poor prognosis of PPCM patients who show no clinical improvement (strength of recommendation IIa). Level of evidence B Treatment with CS or cytotoxic agents was found ineffective [15, 16] . In an RCT trial of 62 patients with new-onset DCM of which some had myocarditis [13] , there was no significant difference in EF improvement between IVIg and placebo group. Nevertheless, in a prospective nonrandomized trial, there was a significant improvement of fractional shortening compared to control. We conclude that further research is warranted regarding IVIg use in myocarditis due to inconclusive results (strength of recommendation IIb). Chronic idiopathic pericarditis (CIP) appears in up to 25% of acute pericarditis cases. It may be associated with viral infections and autoantibodies [21] . There is limited evidence on the role of IVIg as an alternative therapy for prolonged steroid or colchicine treatment in CIP (strength of recommendation IIa). Atherosclerosis is believed to be mediated also by humeral and cellular immune mechanisms. There are accumulating data that support a role of IVIg in prevention of atherosclerosis. Possible mechanisms include decrease of matrix metalloproteinase 9 secretion from mononuclear cells [22], increase of IL-10 [12] , and decrease of oxidized lowdensity lipoprotein uptake by macrophages [23] . Nevertheless, clinical trials are required in order to establish the relationship between IVIg use and atherosclerosis therapy. Level of evidence A It is the leading cause of acquired heart disease in the USA. Kawasaki disease is an FDA-approved absolute indication for IVIg therapy. The frequency of CA aneurysm development and associated morbidity and mortality have been dramatically decreased as a result of IVIg therapy when given within 10 days following the onset of fever. A single dose of 2 g/kg of IVIg over 10 H is usually Level of evidence B Because there is no efficient treatment for established rheumatic carditis, several agents has been proposed in an attempt to change the natural history. IVIg has failed to change clinical outcome and disease progression and therefore is not recommended for treatment of acute rheumatic fever (strength of recommendation III). Level of evidence C Neonatal lupus erythematosus is a rare disease that is associated with anti-Ro and anti-La autoantibodies [26] . A single case series of eight subjects had Level of evidence C IVIg has anti-idiotypic properties, as well as human leukocyte antigen molecules that may neutralize high panel reactive antibodies in sensitized patients awaiting cardiac transplantation. There is some evidence for IVIg benefit in patients with left ventricular assist device who are awaiting cardiac transplantation (strength of recommendation IIa). Nevertheless, IVIg did not reduce sensitization in previously unsensitized patients who underwent Norwood procedure (strength of recommendation III). The following conditions refer to (Table 7) . Level of evidence C Linear IgA bullous disease may affect the eye (in 67% of patients) and may present as chronic cicatrizing conjunctivitis. Systemic disease may be treated with systemic CS and dapsone. In poorly responsive patients, IVIg treatment may be used, although its use should be further investigated (strength of recommendation IIa). Level of evidence C Mucous membrane pemphigoid (MMP) may involve the eye. There is some evidence for the beneficial effect of IVIg in MMP that involves the eye. IVIg may provide more rapid control of symptoms and prevents remissions during long-term follow-up [28, 29] . This notion should be supported by larger randomized trials (strength of recommendation IIa). Level of evidence C There are some but limited data regarding the potential benefit of IVIg use in Behcet's disease. Further study is required. Nevertheless, IVIg should be carefully considered in patients resistant to conventional immunosuppressive therapy (strength of recommendation IIa). Level of evidence A The natural history of optic neuritis in multiple sclerosis patients is not altered by IVIg transfusion, neither clinically nor radiologically. Therefore, IVIg is not recommended in that setting (strength of recommendation III). Level of evidence C There is anecdotal evidence for the possible beneficial role of IVIg in the treatment of inflammatory pseudotumor of orbit (strength of recommendation IIb). Level of evidence C Birdshot retinochoroiditis is a rare inflammatory disease (bilateral autoimmune posterior uveitis of idiopathic origin). Without immunosuppressive treatment, a progressive visual deterioration will occurs in 80% of patients [30] . There is supporting evidence for the use of IVIg, especially in patients unresponsive to other therapies (strength of recommendation IIa). Level of evidence C It is caused by inflammatory process of unknown etiology, which is confined to the orbit. There are very limited data on the effect of IVIg in patients with orbital myositis. Such treatment might be considered in symptomatic patients, resistant to other therapies (strength of recommendation IIa). Level of evidence C Most cases of refractory uveitis (RU) are associated with autoimmune mechanisms. There are some data supporting the use of IVIg in resistant RU, although more research is required in order to establish clinical guidelines (strength of recommendation IIa). Level of evidence B It seems that IVIg is as efficient as CS in the treatment of Graves' ophthalmopathy. Nevertheless, despite similar clinical response to treatment, IVIg was associated with fewer side effects and the study group showed more tolerance towards it. Therefore, we conclude that IVIg should be considered in CS intolerance (strength of recommendation I). Level of evidence C There is limited evidence for the benefit of IVIg in cancer-associated retinopathy. Nevertheless, since spontaneous recovery usually does not occur, IVIg may be used in progressive visual compromise in addition to CS or plasmapheresis (strength of recommendation IIb). The following conditions refer to (Table 8 ). Level of evidence B A few case reports and a single RCT clearly indicate the efficacy of IVIg in the treatment of lupus nephritis. In all cases, patients had a beneficial response to IVIg and a significant improvement of renal function was noted. Therefore, IVIg is recommended as an alternative treatment in lupus nephritis or in cases that conventional immunosuppressive treatment fails (strength of recommendation I). Level of evidence C Although evidence for the use of IVIg in renal transplant rejection is limited to case reports and case series results showed that IVIg may be effective for treating acute or chronic renal transplant rejection. IVIg may improve renal function and reverse Ab-mediated rejection. IVIg may be considered among the treatment options generally together with immunosuppressive therapy (strength of recommendation I). Level of evidence C There is weak evidence indicating significant benefit from the use of IVIg in antineutrophil cytoplasmic antibody (ANCA)-associated RPGN. Several case series and case reports showed that IVIg may improve renal function and therefore is recommended as a potential therapy for ANCA-associated RPGN (strength of recommendation I). Level of evidence C The use of IVIg in BK-virus-associated nephropathy in renal allograft recipient is limited only in a few case reports. Nevertheless, in these cases, IVIg showed significant efficacy and with concomitant reduction of immunosuppression it may be considered as one of the treatment options in this disease (strength of recommendation I). Level of evidence B Results coming from a single-arm nonrandomized study and a prospective cohort study showed that IVIg may be effective in treating severe IgA nephropathy and therefore it may be considered as a possible treatment option. However, RCTs are needed to confirm this efficacy (strength of recommendation I). The efficacy of IVIg in membranous nephropathy was studied in few retrospective trials and a case series. Results from these studies indicate that IVIg may be effective in induction of remission. Although there is no strong evidence, IVIg may be considered as an additional option in treatment of membranous nephropathy (strength of level of evidence C; recommendation I). The following conditions refer to (Table 9 ). Level of evidence B There is some evidence that IVIg have steroid-sparing effect and may be effective as monotherapy and/or adjunctive therapy in patients with previously severe unresponsive pemphigus vulgaris (strength of recommendation IIa). Level of evidence C Adjunctive to standard immunotherapy treatment with IVIg may cause improvement in clinical course and may have steroid-sparing effect in previously steroid-dependent patients with refractory pemphigus foliaceus (strength of recommendation IIa). Level of evidence C In some severe cases of bullous pemphigoid, IVIg was found to be effective as monotherapy and adjunctive therapy as well; it had steroid-sparing effect and led to improvement of quality of life (strength of recommendation IIa). Level of evidence C There is some evidence that IVIg monotherapy may be at least as effective as standard immunosuppressive treatment and lead to quick therapy response and better quality of life (strength of recommendation IIa). Level of evidence C The sparse data of positive effect of IVIg on severe cases of epidermolysis bullosa acquisita, linear IgA disease, and pemphigoid gestationis were published (strength of recommendation IIa). Summary In autoimmune blistering diseases, the treatment with IVIg may be effective and has to be implicated in cases with severe disease, resistant to conventional therapy or those who experienced severe complications of such therapy. Level of evidence C The randomized studies have not been performed and the current knowledge about effectiveness of IVIg in SJS and TEN is based on results of multiple prospective noncontrolled studies, retrospective case series, and case reports. The data are limited and inconclusive (strength of recommendation IIb). Level of evidence B The current data based on single, randomized, controlled, and evaluator-blinded trial and number of prospective noncontrolled studies suggest that IVIg may be effective as monotherapy in pediatric patients and as adjunctive therapy in adults. However, in view of the low-cost effectiveness of IVIg, this treatment should be used in cases of severe disabling atopic dermatitis (strength of recommendation IIa). Level of evidence C A number of case reports and case series describe the beneficial effect of IVIg in chronic idiopathic and autoimmune urticaria, but randomized controlled studies are still lacking. The use of IVIg has to be limited to severe unresponsive cases of chronic urticaria or in case of severe complications of conventional treatment (strength of recommendation IIa). Level of evidence C Only three cases of severe resistant psoriasis with psoriatic arthritis responsive to treatment with high-dose immunoglobulin were reported. We conclude that there is now evidence of effectiveness of IVIg in psoriasis (strength of recommendation IIb). Level of evidence C IVIg was successfully used in few cases of previously unresponsive pyoderma gangrenosum, but its systematic use cannot be recommended (strength of recommendation IIa). Level of evidence C Several case reports and case series showed IVIg to be effective for nephrogenic fibrosing dermopathy, pretibial myxedema, and Arndt-Gottron scleromyxedema, but still well-controlled studies are lacking. We suppose that IVIg can be used in severe cases of these rare conditions, unresponsive to conventional treatment (strength of recommendation IIa). The following conditions refer to (Table 10 ). Retrospective series report [299] No difference in length of stay, mechanical ventilation, severity of inflammatory response or incidence of sepsis, wound progression, time to healing, and mortality 16 TEN patients with initial rash involving 65±29%, treated with IVIg vs. 16 patients with TEN initial rash involving 65±27% not treated with IVIg IVIg (Gamimune® N, Bayer Inc., Toronto, CA) 0.2 to 0.7 g/kg per day according to discretion of attending physician on duty, as 5% or 10% solution according to availability, for 4±1 day Retrospective [300] No difference of SCORAD index and in global evaluation of disease severity by patients at day 30 10 adult patients (mean age 28) with sever atopic dermatitis IVIg 1 g/kg per day (Sandoglobulin®, Sandoz, France) immediate or delayed by 1 month (meanwhile intensive therapy with emollients and topical CS (limited to class II 60 g/month)), for 2 days in 8-h infusion, as monotherapy RC evaluatorblinded trial [301] Atopic dermatitis Improvement in skin score (mEASI) was apparent in responders (4/6 patients) from 2 to 3 months and continued to improve over a 6-month period; after 7 months, there was a significant reduction of the overall mEASI; CD69-expressing T cells decreased to 60% from baseline; no change of TNF-a and IFN-g 6 adult patients with severe stable atopic dermatitis Flebogamma® 5% 2 g/kg per month given in 2-5 days for 6 months as adjunctive treatment, followed for 3 months Open, single center, prospective [302] 3/3 patients improved skin scores, allowing reduction of steroid dose 3 adult patients with severe atopic dermatitis and steroid-related side effects Alphaglobin® (Grifols, UK) or Sandoglobulin ® (Novartis, UK) 2 g/kg per month in 3-5 days adjunctive to CS Case report [303] Clinic Rev Allerg Immunol (2010) 38:201-269 Case report [318] First patient had significant reduction in skin scores (36/60 to 11/60) for 1 year only; second had a dramatic sustained response with continued Tx (interval subsequently increased to 10 weeks) 2 patients with scleromyxedema and severe skin disease IVIg 0.4 g/kg per day for 5 days, monthly Case report [319] Improvement after the first treatment, continuous skin softening and reduction of induration, sustained response to treatment after 20 courses A 48-year-old female with long-standing scleromyxedema unresponsive to highdose CS and immunosuppressive (CP, melphalan) treatment IVIg 2 g/kg in 2 days (Intratect®; Biotest, Dreieich, Germany) every 4 weeks, adjunctive to PD 10 mg/day Case report [320] Progressive clinical improvement over several months allowing discontinuation of PD but rapid deterioration afterwards with lethal CVA despite reinstating PD and CP An 81-year-old female with scleromyxedema and IDDM IVIg (Gamimune N, 10%, Bayer) 1.5 g/ kg (dose reduced due to CHF) every 4 weeks and oral PD 30 mg/day Case report [321] A positive response after 2 cycles An 82-year-old female with a 12-year history of scleromyxedema unresponsive to various preceding therapies Venimmun® N (ZLB Behring, Germany) 0.5 g/kg for 5 days at 4-week intervals as monotherapy Case report [322] Marked clinical improvement, maintained with repeated IVIg infusions A 56-year-old woman with scleromyxedema IVIg (Sandoglobulin®) 2 g/kg over 5 days as monotherapy Case report [323] Complete clearance of skin lesions, sustained effect after 1 year without treatment Case report [324] Clinic Rev Allerg Immunol (2010) 38: Kaposi's sarcoma Level of evidence C A patient with polymyositis and Kaposi sarcoma had remission of both conditions on IVIg therapy (strength of recommendation IIb). Level of evidence C Stabilization of metastatic melanoma was shown in the small group of patients after addition of IVIg to standard therapy (strength of recommendation IIb). Level of evidence CIVIg was shown to be effective in preventing severe recurrent chemotherapy-induced oral mucositis in two patients treated with methotrexate (strength of recommendation IIa). Level of evidence C Anecdotal case report describes complete remission of metastatic malignant thymoma after four cycles of IVIg given to myasthenic patient (strength of recommendation IIb). Level of evidence C After thymectomy, two patients with Good syndrome were maintained with IVIg for developed immunodeficiency; one of them developed Kaposi sarcoma after 3 years (strength of recommendation IIb). The following conditions refer to (Table 11) . Summary There are still no randomized controlled trials evaluating efficacy of IVIg and it cannot be recommended for treatment of epithelial or other solid malignancies. Level of evidence C There is some evidence that IVIg therapy can improve the Neuropathy Impairment Score in patients with diabetic demyelinating polyneuropathy (strength of recommendation IIa). A few case reports describe regression of symptoms of proximal diabetic neuropathy, diabetic amyotrophy, and cranial nerve neuropathy in different diabetic patients treated with IVIg (strength of recommendation IIa). We conclude that evidence for the use of IVIg in diabetic neuropathies is poor and its systematic use cannot be recommended. Disease Improvement in all but relapse in 1 patient, 2 weeks to 6 months for full response, most needing 6-8 weekly cycles 10 patients, 30-79 years old with scleromyxedema IVIg 2 g/kg per month given over 5 days; Octagam® (2 patients), Sandoglobulin® (3 patients), Gammagard ®SD (1 patient), unknown (2patients); adjunctive to PD (2 patients) and thalidomide (1 patient) or as monotherapy (7 patients) Review of published case reports [325] Regrowth of eyelashes, eyebrows, and body and scalp hair after second dose, significant hair regrowth with 5-6 cm of scalp hair Level of evidence B Therapeutic efforts including dietary therapy and immunomodulation with IVIg fail to improve prognosis in patients with X-linked adrenoleukodystrophy and BMT remains the only treatment that can reverse early neurological manifestations and adrenal impairment of ALD (strength of recommendation III). Level of evidence C No evidence supports the use of IVIg in Waterhouse-Friderichsen syndrome due to meningococcal sepsis (strength of recommendation III). Level of evidence C No evidence supports the use of IVIg in autoimmune polyendocrine syndrome type 2 (strength of recommendation IIb). The following conditions refer to (Table 12) . Level of evidence C There is weak evidence coming out from several case reports that IVIg may be a useful treatment option either as a combination therapy with CS or in cases that steroid treatment fails (strength of recommendation I). Level of evidence B Taking into consideration the limited evidence (one RCT) and the unfavorable effect of IVIg treatment, at this point, IVIg should not be used as treatment of adrenoleukodystrophy (strength of recommendation III). Level of evidence C No benefit was observed from the use of IVIg in two case series. Considering the weak evidence and the negative outcome, IVIg is not recommended for the treatment of amyotrophic lateral sclerosis (strength of recommendation III). Level of evidence C The use of IVIg in autism is only limited to case series and the effect is questionable. IVIg is not recommended at the moment for the treatment of autism (strength of recommendation III). Level of evidence A Several RCTs evaluated the effectiveness of IVIg. The results of these studies are strongly pointing to the useful effect of IVIg in patients with chronic inflammatory demyelinating polyneuropathy. IVIg should be considered as an additional option in combination with other immunosuppressive agents (strength of recommendation I). Level of evidence C In this rare syndrome, IVIg was reported in several case reports and a retrospective study proved that it induced significant response. Although there is no strong evidence, IVIg may be considered as an additional option in treatment of opsoclonus myoclonus (strength of recommendation I). Level of evidence B Results coming from one small RCT testing the effect of IVIg showed significant improvement in symptoms; therefore, IVIg is recommended as an additional option for treatment of PANDAS (strength of recommendation I). Level of evidence A Data from several RCTs and a metaanalysis showed significant differences between IVIg and placebo favoring the use of IVIg in relapsing-remitting multiple sclerosis (MS). On the other hand, a recent RCT including 127 patients with relapsing-remitting MS treated with IVIg or placebo showed no significant difference in the proportion of relapse-free patients among treated groups. Another recent RCT including 231 patients showed that IVIg can delay progression of disease in primary chronic progressive MS but no significant difference in progression was noted for secondary chronic progressive MS. To conclude, IVIg may be used as an alternative therapy in relapsingremitting MS and in primary chronic progressive MS when standard immunosuppression therapy fails (strength of recommendation IIb). Level of evidence A There is strong evidence, several randomized controlled trials, and a meta-analysis that prove that IVIg is of benefit in improving the disability grade in patients with Guillain-Barré syndrome. No significant difference between IVIg and PP was found. IVIg should be considered as a treatment option in Guillain-Barré syndrome (strength of recommendation I). Level of evidence A There is no reliable evidence to recommend the use of IVIg in paraproteinemic neuropathy. A restricted number of RCT's and a systematic review showed only modest benefit with IVIg in the short term (strength of recommendation IIb). Level of evidence B A single small RCT showed significant improvement in patients suffering from Lambert-Eaton myasthenic syndrome with the use of IVIg compared to placebo. Therefore, it is acceptable to consider the use of IVIg in this rare and severe neurological syndrome (strength of recommendation I). Level of evidence B Data from a small randomize control trial and several case reports showed that the use of IVIg led to significant improvement in patients with stiff-person syndrome and was superior to placebo. IVIg should be considered as a treatment option in this syndrome especially if the first-line treatment fails (strength of recommendation I). Level of evidence A Two RCTs investigated the efficacy of IVIg in patients with intractable childhood epilepsy compared with placebo. Results from these studies do not support benefit from the use of IVIg. Therefore, IVIg is not recommended for the treatment of intractable childhood epilepsy (strength of recommendation III). Level of evidence C There is no reliable evidence (level of evidence C-III) to recommend the use of IVIg in the treatment of critical illness polyneuropathy (strength of recommendation III). Level of evidence A Several RCTs and a meta-analysis examined the efficacy of IVIg in patient with myasthenia gravis. Results are conflicting. A recent metaanalysis concluded that there is insufficient evidence to determine the efficacy of IVIg in myasthenia gravis. IVIg may be used as treatment for myasthenia gravis severe acute exacerbations (strength of recommendation IIa). The following conditions refer to (Table 13 ). Level of evidence B Retrospective analyses revealed that IVIg is beneficial in terms of reduction of acute and chronic infections and days of stay in the hospital. Intravenous route is preferred over intramuscular administration of immunoglobulin and the number and severity of complications are inversely correlated with the dose of IVIg (strength of recommendation I). Level of evidence C Despite relatively low evidence of effectiveness of IVIg, the majority of WAS patients are treated with IVIg, which appears to be effective in reduction of acute and chronic infections in these immunodeficient patients (strength of recommendation IIa). Level of evidence C There is weak evidence that IVIg is useful in the treatment of hyper-IgE syndrome. IVIg may be tried in cases in which recurrent live-threatening diseases cannot be controlled by antibiotic prophylaxis (strength of recommendation IIb). Level of evidence C There is scarce evidence that IVIg is useful in the treatment of IgG subclass deficiencies. Most of the experience reported is patients with IgG2 deficiency. In our opinion, when antibiotic treatment is not effective, IVIg would be a reasonable alternative (strength of recommendation IIb). Level of evidence B This is a heterogeneous group. Specific deficiency of antibodies after vaccination has been found to correlate with infection susceptibility. Most of the published experience regarding IVIg is in patients with deficiency of antibodies to capsular polysaccharide. IVIg has been reported to be beneficial in some cases. This is not surprising as antibodies to bacterial capsular polysaccharide are contained in IVIg [31] . The evidence for the use of IVIg in specific antibody deficiency is not strong but might be warranted when recurrent infection is present and it is possible to demonstrate low antibody responses to a relevant vaccine (strength of recommendation IIa). Level of evidence B The hyper-IgM syndrome (HIGM) is a rare hereditary immune deficiency, characterized by a low or nil level of IgG and IgA and a normal or increased level of IgM, predominately affecting boys. Its clinical manifestations are dominated by recurrent infection, notably of the digestive tube, the ears, nose, and throat and the lungs. IVIg may be considered to treat patients with HIGM and recurrent infections (strength of recommendation I). Level of evidence C Transient hypogammaglobulinemia of infancy is characterized by a prolongation and accentuation of the physiologic hypogammaglobulinemia normally occurring during the first 3 to 6 months of life and recovers spontaneously between 18 and 36 months of age. Infants with transient hyogammaglobulinemia of infancy (THI) may remain asymptomatic or develop recurrent sinopulmonary infections, but severe or lifethreatening infections are rare. In general, supportive and antimicrobial therapies are sufficient management for the treatment of specific infections in patients with THI. In cases in which infections are severe or refractory to conventional therapy, IVIg is sometimes considered although literature reports are lacking (strength of recommendation I). Level of evidence B SCID is a severe form of heritable immunodeficiency in which both "arms" of the adaptive immune system are defected. These babies, if untreated, usually die within 1 year due to severe recurrent infections. Treatment with BMT is successful, and IVIg is used as an adjuvant for this therapy (strength of recommendation I). Many different genetic diseases will ultimately result in primary phagocytic defect: cyclic neutropenia, severe congenital neutropenia, Shwachman-Diamond syndrome, leu-kocyte adhesion deficiency, Rac2 deficiency, interferon-γ and IL-12 defects, chronic granulomatous disease, myeloperoxidase deficiency, Chediak-Higashi syndrome, and neutrophil-specific granule deficiency [34] . An extensive PubMed-based search revealed little if any information regarding the efficacy of IVIg in the above entities. IgA deficiency may be associated with preventable anaphylaxis or anaphylactoid reaction following IVIg transfusion [35] . This adverse reaction is encountered in patients with selective IgA deficiency and high titer of anti-IgA antibodies. In those patients, anaphylaxis can be avoided by the use of IgA-depleted IVIg preparation [36] . This article summarizes most of the studies dealing with IVIg administration that were publicized until recently. We have included an array of clinical conditions, some in which the use of IVIg is expected according to their pathogenesis, such as primary immunodeficiencies and rheumatic diseases, and others somewhat less obvious indications including cardiac and oncologic diseases. In some diseases, the usage of IVIg was found to be highly recommended (with a level of evidence A and strength of recommendation I): Kawasaki disease, acquired hypogammaglobulinemia, juvenile rheumatoid arthritis, hemolytic disease of the newborn, acute immune thrombocytopenic purpura, chronic inflammatory demyelinating polyneuropathy, and Guillain-Barré syndrome. For many other diseases, treatment with IVIg was found effective as well, but this was less well established, either due to a lack of well-designed studies or due to conflicting evidence among them. In some diseases, there is a strong recommendation against using IVIg (with a level of evidence A and strength of recommendation III): stem cell/bone marrow transplantation, inclusion body myositis, recurrent pregnancy loss due to antiphospholipid syndrome, optic neuritis, and intractable childhood epilepsy. Nevertheless, the effectiveness of IVIg in such a large span of diseases fortifies the accumulating evidence that many pathological conditions are autoimmune mediated. High-dose intravenous gamma globulin therapy of refractory, in particular idiopathic thrombocytopenia in childhood ACC/ AHA guidelines for the evaluation and management of chronic heart failure in the adult: executive summary. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure): developed in collaboration with the International Society for Heart and Lung Transplantation Review: intravenous immunoglobulin therapy and thromboembolic complications Intravenous immunoglobulin: adverse effects and safe administration Intravenous immunoglobulin and the kidney-a two-edged sword Acquired von Willebrand syndrome: data from an international registry Treatment of acquired von Willebrand syndrome in patients with monoclonal gammopathy of uncertain significance: comparison of three different therapeutic approaches Transient neutropenia induced by intravenous immune globulin Randomized trial of anti-D immunoglobulin versus low-dose intravenous immunoglobulin in the treatment of childhood chronic idiopathic thrombocytopenic purpura Single dose of anti-D immune globulin at 75 microg/kg is as effective as intravenous immune globulin at rapidly raising the platelet count in newly diagnosed immune thrombocytopenic purpura in children New hope for treatment of neonatal haemochromatosis Complement activation in patients with congestive heart failure: effect of high-dose intravenous immunoglobulin treatment Controlled trial of intravenous immune globulin in recent-onset dilated cardiomyopathy Immunomodulating therapy with intravenous immunoglobulin in patients with chronic heart failure Successful highdose intravenous immunoglobulin therapy for a patient with fulminant myocarditis The current status of immune modulating therapy for Intravenous immunoglobulins for adult Still's disease and pregnancy Intravenous immunoglobulin for ANCAassociated systemic vasculitis with persistent disease activity Pooled intravenous immunoglobulin in the management of systemic vasculitis Treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis with high-dose intravenous immunoglobulin Serologic and clinical response to treatment of systemic vasculitis and associated autoimmune disease with intravenous immunoglobulin Intravenous immunoglobulin as sole therapy for systemic vasculitis Intravenous immunoglobulin (IVIg) therapy in MPO-ANCA related polyangiitis with rapidly progressive glomerulonephritis in Japan Long term effectiveness of intravenous immunoglobulin in Churg-Strauss syndrome Treatment of Churg-Strauss syndrome with high-dose intravenous immunoglobulin Efficacy of intravenous immunoglobulin therapy in a case of autoimmunemediated chronic active hepatitis Intravenous immunoglobulin plus interferon-alpha in autoimmune hepatitis C High-dose immunoglobulin therapy for severe IgA nephropathy and Henoch-Schönlein purpura Intravenous immunoglobulin therapy for severe digestive manifestations of Henoch-Schönlein purpura Successful treatment of adult-onset Henoch-Schönlein purpura nephritis with high-dose immunoglobulins Henoch-Schönlein nephritis. Adverse effect of treatment with intravenous immunoglobulin Intravenous immunoglobulin in Henoch-Schönlein purpura Fasciitis in mixed connective tissue disease successfully treated with highdose intravenous immunoglobulin Efficacy of pulsed intravenous immunoglobulin therapy in mixed connective tissue disease Intravenous immunoglobulin modulates cutaneous involvement and reduces skin fibrosis in systemic sclerosis: an open-label study High-dose intravenous immunoglobulin infusion as treatment for diffuse scleroderma Intravenous immunoglobulins improve the function and ameliorate joint involvement in systemic sclerosis: a pilot study Skin score decrease in systemic sclerosis patients treated with intravenous immunoglobulin-a preliminary report Intravenous immunoglobulin in the treatment of polyarticular juvenile rheumatoid arthritis: a phase I/II study. Pediatric Rheumatology Collaborative Study Group Therapeutical and immunological effects of methylprednisolone pulse therapy in comparison with intravenous immunoglobulin. Treatment in patients with juvenile chronic arthritis Intravenous immunoglobulin therapy in systemic onset juvenile rheumatoid arthritis: a follow-up study High dose immunoglobulin therapy in severe juvenile chronic arthritis: long-term follow-up in 16 patients Failure of low-dose intravenous immunoglobulin therapy to suppress disease activity in patients with treatment-refractory rheumatoid arthritis Immunomodulating therapy of rheumatoid arthritis by high-dose intravenous immunoglobulin High dose intravenous immunoglobulin (IVIg) in severe refractory rheumatoid arthritis: no evidence for efficacy Successful treatment of 'malignant rheumatoid arthritis' in Japan with pooled intravenous immunoglobulin Benefit of IVIG for long-standing ataxic sensory neuronopathy with Sjögren's syndrome. IV immunoglobulin Intravenous immunoglobulin treatment in painful sensory neuropathy without sensory ataxia associated with Sjögren's syndrome Intravenous immunoglobulin therapy in sensory neuropathy associated with Sjögren's syndrome A controlled trial of high-dose intravenous immune globulin infusions as treatment for dermatomyositis Intravenous immunoglobulin treatment in autoimmune diseases Efficacy of high-dose intravenous immunoglobulin therapy in Japanese patients with steroid-resistant polymyositis and dermatomyositis A controlled study of intravenous immunoglobulin combined with prednisone in the treatment of IBM High-dose immunoglobulin therapy in sporadic inclusion body myositis: a double-blind, placebo-controlled study Treatment of inclusion-body myositis with IVIg: a double-blind, placebo-controlled study Intravenous immunoglobulin therapy for resistant ocular Behcet's disease Behcet's syndrome treated with highdose intravenous IgG and low-dose aspirin A prospective study of treatment of acquired (autoimmune) factor VIII inhibitors with high-dose intravenous gamma globulin Low response to high-dose intravenous immunoglobulin in the treatment of acquired factor VIII inhibitor Intravenous immunoglobulin therapy for acquired coagulation inhibitors: a critical review Combined prednisolone and intravenous immunoglobulin treatment for acquired factor VIII inhibitors: a 2-year review Prophylaxis against infections with low-dose intravenous immunoglobulins (IVIG) in chronic lymphocytic leukemia. Results of a crossover study Crossover study of immunoglobulin replacement therapy in patients with low-grade B-cell tumors Randomized trial of intravenous immunoglobulin prophylaxis for patients with chronic lymphocytic leukaemia and secondary hypogammaglobulinaemia Randomised trial of intravenous immunoglobulin as prophylaxis against infection in plateau-phase multiple myeloma. The UK Group for Immunoglobulin Replacement Therapy in Multiple Myeloma Immunoglobulin prophylaxis during intensive treatment of acute lymphoblastic leukemia in children Treatment of fever and neutropenia with antibiotics versus antibiotics plus intravenous gamma globulin in childhood leukemia Immunoglobulin replacement in chronic lymphocytic leukaemia Prophylaxis against infections with intravenous immunoglobulins in multiple myeloma Hypogammaglobulinaemia in low grade B cell tumours; significance and therapy Pure red cell aplasia: treatment with intravenous immunoglobulin concentrate Treatment of pure red cell aplasia by high dose intravenous immunoglobulins Dose-by-dose virological and hematological responses to intravenous immunoglobulin in an immunocompromised patient with persistent parvovirus B19 infection Pure red cell aplasia due to parvovirus B19 infection after liver transplantation: a case report and review of the literature Acute renal failure in a pediatric kidney allograft recipient treated with intravenous immunoglobulin for parvovirus B19 induced pure red cell aplasia Pure red cell aplasia due to parvovirus following treatment with CHOP and rituximab for B-cell lymphoma Relapsing pure red cell aplasia associated with B-cell chronic lymphocytic leukemia successfully treated by intravenous immunoglobulin concentrate A case of persistent anemia in a renal transplant recipient: association with parvovirus B19 infection Fulminant parvovirus infection following erythropoietin treatment in a patient with acquired immunodeficiency syndrome Chronic pure red cell aplasia caused by parvovirus B19 in AIDS: use of intravenous immunoglobulin-a report of eight patients Successful treatment of persistent erythroid aplasia caused by parvovirus B19 infection in a patient with common variable immunodeficiency with lowdose immunoglobulin Red cell aplasia caused by parvovirus B19 in AIDS: use of i.v. immunoglobulin Parvovirus B19 in HIV infection: a treatable cause of anemia Management of persistent B19 parvovirus infection in AIDS Chronic idiopathic pure red cell aplasia: successful treatment during pregnancy and durable response to intravenous immunoglobulin Pure red cell aplasia associated with systemic lupus erythematosus: remission after a single course of intravenous immunoglobulin Parvovirus B19-induced red cell aplasia treated with plasmapheresis and immunoglobulin Treatment of antibody-mediated pure red-cell aplasia with high-dose intravenous gamma globulin Persistent parvovirus B19 infection and pure red cell aplasia in Waldenstrom's macroglobulinemia: successful treatment with high-dose intravenous immunoglobulin Clinical significance of inhibitors in acquired von Willebrand syndrome Three cases of acquired von Willebrand disease associated with systemic lupus erythematosus Intravenous immunoglobulin in the treatment of aplastic anemia Transient aplastic anemia caused by parvovirus B19 infection in a heart transplant recipient Treatment of hematologic disorders other than immune thrombocytopenic purpura with intravenous immunoglobulin (IVIg)-report of seven cases and review of the literature Efficacy of intravenous immunoglobulin in the treatment of autoimmune hemolytic anemia: results in 73 patients Diagnosis and clinical course of autoimmune neutropenia in infancy: analysis of 240 cases Use of intravenous gamma globulin for the treatment of autoimmune neutropenia of childhood and autoimmune hemolytic anemia Evans syndrome: results of a national survey Evans syndrome. Results of a pilot study utilizing a multiagent treatment protocol Intravenous gamma globulin for thrombocytopenia in children with Evans syndrome Induction of remission with intravenous immunoglobulin and cyclophosphamide in steroid-resistant Evans' syndrome associated with dermatomyositis Fetomaternal alloimmune thrombocytopenia: antenatal therapy with IvIgG and steroids-more questions than answers. European Working Group on FMAIT Should immunoglobulin therapy be used in allogeneic stem-cell transplantation? A randomized, double-blind, dose effect, placebocontrolled, multicenter trial A randomized trial of high dose polyvalent intravenous immunoglobulin (HDIgG) vs. cytomegalovirus (CMV) hyperimmune IgG in allogeneic hemopoietic stem cell transplants (HSCT) A controlled trial of long-term administration of intravenous immunoglobulin to prevent late infection and chronic graft-vs.-host disease after marrow transplantation: clinical outcome and effect on subsequent immune recovery Intravenous immunoglobulin and CMV-seronegative blood products for prevention of CMV infection and disease in bone marrow transplant recipients A multicenter, randomized, double-blind comparison of different doses of intravenous immunoglobulin for prevention of graft-versus-host disease and infection after allogeneic bone marrow transplantation High-dose weekly intravenous immunoglobulin to prevent infections in patients undergoing autologous bone marrow transplantation or severe myelosuppressive therapy. A study of the American Bone Marrow Transplant Group Immunomodulatory and antimicrobial efficacy of intravenous immunoglobulin in bone marrow transplantation Immunoglobulin infusion for isoimmune haemolytic jaundice in neonates Systematic review of intravenous immunoglobulin in haemolytic disease of the newborn High-dose intravenous immunoglobulin in non-ABO transfusion incompatibility Haemolytic transfusion reaction-successful attenuation with methylprednisolone and high dose immunoglobulin Hyperhemolytic transfusion reaction in sickle cell disease Use of intravenous immunoglobulin and intravenous methylprednisolone in hyperhaemolysis syndrome in sickle cell disease Post-transfusion hyperhaemolysis in a patient with sickle cell disease: use of steroids and intravenous immunoglobulin to prevent further red cell destruction The use of intravenous gamma globulin in the treatment of typical hemolytic uremic syndrome High-dose intravenous gamma globulin infusions in hemolytic-uremic syndrome: a preliminary report Treatment of thrombotic thrombocytopenic purpura with high-dose immunoglobulins. Results in 17 patients. Italian Cooperative Group for TTP Efficacy of intravenous immunoglobulin in the treatment of thrombotic thrombocytopaenic purpura. A study of 44 cases High-dose intravenous gamma-globulins for heparininduced thrombocytopenia: a prompt response The therapy of the heparin-induced thrombosis-thrombocytopenia syndrome with immunoglobulins An evaluation of intravenous immunoglobulin in the treatment of human immunodeficiency virus-associated thrombocytopenia Intravenous immunoglobulin or high-dose methylprednisolone, with or without oral prednisone, for adults with untreated severe autoimmune thrombocytopenic purpura: a randomised, multicentre trial The comparison of gamma globulin to steroids in treating adult immune thrombocytopenia. An interim analysis A prospective, randomized trial of high-dose intravenous immune globulin G therapy, oral prednisone therapy, and no therapy in childhood acute immune thrombocytopenic purpura Clinical course of children with immune thrombocytopenic purpura treated with intravenous immunoglobulin G or megadose methylprednisolone or observed without therapy Intravenous immunoglobulin in the treatment of human immunodeficiency virus-related thrombocytopenia Usefulness of a low-dose intravenous immunoglobulin regimen for the treatment of thrombocytopenia associated with AIDS Clinical efficacy and safety of a novel intravenous immunoglobulin preparation in adult chronic ITP Treatment of adult chronic autoimmune thrombocytopenic purpura with repeated high-dose intravenous immunoglobulin High-dose intravenous immunoglobulin for posttransfusion purpura High-dose intravenous immunoglobulin for post-transfusion purpura Post-transfusion purpura following open heart surgery: management by high dose intravenous immunoglobulin infusion High-dose immunoglobulin therapy in renal transplant recipients with hemophagocytic histiocytic syndrome Hemophagocytic syndrome: a review of 18 pediatric cases Immunomodulation treatment for childhood virus-associated haemophagocytic lymphohistiocytosis Infection associated hemophagocytic syndrome: a report of 50 children Intravenously administered immune globulin for the treatment of infection-associated hemophagocytic syndrome Successful treatment of cytomegalovirus-associated hemophagocytic syndrome by intravenous immunoglobulins Rapidly deteriorating polyneuropathy associated with osteosclerotic myeloma responsive to intravenous immunoglobulin and radiotherapy Poor response to intravenous immunoglobulin therapy in patients with Castleman's disease and the POEMS syndrome Intravenous immunoglobulin therapy in POEMS syndrome: a case report Successful treatment of post-transplant lymphoproliferative disorder with interferon-alpha and intravenous immunoglobulin Cytomegalovirus prophylaxis with intravenous polyvalent immunoglobulin in high-risk renal transplant recipients The National Institute of Child Health and Human Developments Intravenous Immunoglobulin Study Group (1991) Intravenous immune globulin for the prevention of bacterial infections in children with symptomatic human immunodeficiency virus infection Intravenous immunoglobulin in symptomatic and asymptomatic children with perinatal HIV infection Plasmodium falciparum: diversity of isolates from Malawi in their cytoadherence to melanoma cells and monocytes in vitro Parasitologic and clinical human response to immunoglobulin administration in falciparum malaria Intravenous immunoglobulin for post-polio syndrome: a randomised controlled trial Post-polio syndrome patients treated with intravenous immunoglobulin: a double-blinded randomized controlled pilot study Effect of intravenous immunoglobulin in patients with post-polio syndrome-an uncontrolled pilot study Polyclonal intravenous immunoglobulin for the treatment of severe sepsis and septic shock in critically ill adults: a systematic review and meta-analysis Possible benefit of intravenous immunoglobulin therapy in a lung transplant recipient with West Nile virus encephalitis Treatment of West Nile virus encephalitis with intravenous immunoglobulin Prophylactic intravenous administration of standard immune globulin as compared with core-lipopolysaccharide immune globulin in patients at high risk of postsurgical infection Polyvalent immunoglobulins for prophylaxis of bacterial infections in patients following multiple trauma. A randomized, placebo-controlled study Prophylactic intravenous immunoglobulin replacement in high-risk burn patients Safety and efficacy of intravenous immunoglobulin prophylaxis in pediatric head trauma patients: a double-blind controlled trial Prevention of infection in multiple trauma patients by high-dose intravenous immunoglobulins Reduced incidence of postoperative infection after intravenous administration of an immunoglobulin A-and immunoglobulin Menriched preparation in anergic patients undergoing cardiac surgery Immunoglobulin replacement in patients with chronic lymphocytic leukaemia: a comparison of two dose regimes Clinical experience with 20 cases of group A streptococcus necrotizing fasciitis and myonecrosis: 1995 to 1997 Successful management of severe group A streptococcal soft tissue infections using an aggressive medical regimen including intravenous polyspecific immunoglobulin together with a conservative surgical approach High-dose immunoglobulin-life-saving in invasive group A streptococcal infection Group A streptococcal bacteraemia and necrotizing fasciitis in a renal transplant patient: a case for intravenous immunoglobulin therapy The effect of intravenous immunoglobulin treatment in recurrent acute otitis media Effect of intravenous gamma globulin therapy in IgG2 deficient and IgG2 sufficient children with recurrent infections and poor response to immunization with Haemophilus influenzae type b capsular polysaccharide antigen Prophylaxis of intravenous immunoglobulin and acyclovir in perinatal varicella Experience of intravenous immunoglobulin and acyclovir in neonates at risk for severe varicella infection-report of five cases Two cases of severe adult varicella pneumonia Varicella pneumonia in a healthy adult presenting with severe respiratory failure Intravenous immunoglobulin in adult varicella pneumonia complicated by acute respiratory distress syndrome Varicella pneumonia complicated by acute respiratory distress syndrome in an adult Intravenous gamma globulin therapy for thrombocytopenic purpura associated with active varicella infection An adult patient with varicella preceded by acute thrombocytopenia High-dose immunoglobulin during pregnancy for recurrent neonatal haemochromatosis Use of intravenous immunoglobulin for treatment of recurrent miscarriage: a systematic review Immunotherapy for recurrent miscarriage Intravenous immunoglobulin (IVIG) and recurrent spontaneous pregnancy loss A randomized, double-blind, placebo-controlled trial of intravenous immunoglobulin in the prevention of recurrent miscarriage: evidence for a therapeutic effect in women with secondary recurrent miscarriage Critical analysis of intravenous immunoglobulin therapy for recurrent miscarriage Short-term therapy for recurrent abortion using intravenous immunoglobulins: results of a double-blind placebo-controlled Italian study Intravenous immunoglobulin for treatment of recurrent pregnancy loss Placebocontrolled trial of treatment of unexplained secondary recurrent spontaneous abortions and recurrent late spontaneous abortions with i Intravenous immunoglobulin in the prevention of recurrent miscarriage Prevention of recurrent miscarriage for women with antiphospholipid antibody or lupus anticoagulant Randomized study of subcutaneous low molecular weight heparin plus aspirin versus intravenous immunoglobulin in the treatment of recurrent fetal loss associated with antiphospholipid antibodies A multicenter, placebo-controlled pilot study of intravenous immune globulin treatment of antiphospholipid syndrome during pregnancy. The Pregnancy Loss Study Group Pregnancy outcome in recurrent spontaneous abortion associated with antiphospholipid antibodies: a comparative study of intravenous immunoglobulin versus prednisone plus low-dose aspirin Pregnancy complicated by the antiphospholipid syndrome: outcomes with intravenous immunoglobulin therapy The selective use of heparin/aspirin therapy, alone or in combination with intravenous immunoglobulin G, in the management of antiphospholipid antibody-positive women undergoing in vitro fertilization Recurrent first trimester spontaneous abortion associated with antiphospholipid antibodies: a pilot study of treatment with intravenous immunoglobulin Normal fetal growth in women with antiphospholipid syndrome treated with high-dose intravenous immunoglobulin (IVIG) The effect of antenatal intravenous immunoglobulin on ascending intrauterine infection after preterm premature rupture of the membranes: a pilot study Is intravenous immunoglobulins (IVIG) efficacious in early pregnancy failure? A critical review and meta-analysis for patients who fail in vitro fertilization and embryo transfer (IVF) Treatment of repeated unexplained in vitro fertilization failure with intravenous immunoglobulin: a randomized, placebo-controlled Canadian trial Intravenous immune globulin in the therapy of peripartum cardiomyopathy Treatment of acute inflammatory cardiomyopathy with intravenous immunoglobulin ameliorates left ventricular function associated with suppression of inflammatory cytokines and decreased oxidative stress Gamma-globulin treatment of acute myocarditis in the pediatric population The prevention of coronary artery aneurysm in Kawasaki disease: a meta-analysis on the efficacy of aspirin and immunoglobulin treatment The treatment of Kawasaki syndrome with intravenous gamma globulin Treatment of Kawasaki disease with a moderate dose (1 g/kg) of intravenous immunoglobulin Clinical responses of patients with Kawasaki disease to different brands of intravenous immunoglobulin Therapeutic effectiveness of intravenous immunoglobulin at 1 g/kg and 2 g/kg on Kawasaki disease: a comparative and follow-up study A randomized prospective study on the use of 2 g-IVIG or 1 g-IVIG as therapy for Kawasaki disease A single intravenous infusion of gamma globulin as compared with four infusions in the treatment of acute Kawasaki syndrome Intravenous immunoglobulin in acute rheumatic fever: a randomized controlled trial Intravenous immunoglobulin reduces anti-HLA alloreactivity and shortens waiting time to cardiac transplantation in highly sensitized left ventricular assist device recipients Low-dose prophylactic intravenous immunoglobulin does not prevent HLA sensitization in left ventricular assist device recipients Failure of prophylactic intravenous immunoglobulin to prevent sensitization to cryopreserved allograft tissue used in congenital cardiac surgery Linear IgA bullous disease limited to the eye: a diagnostic dilemma: response to intravenous immunoglobulin therapy A randomized trial of intravenous immunoglobulin in inflammatory demyelinating optic neuritis A double-blind, randomized trial of IV immunoglobulin treatment in acute optic neuritis Successful intravenous immunoglobulin therapy for resistant inflammatory pseudotumor of the orbit Efficacy of intravenous immunoglobulin in the treatment of Birdshot retinochoroiditis Successful treatment of orbital myositis with intravenous immunoglobulins The treatment of refractory uveitis with intravenous immunoglobulin Efficacy of intravenous immunoglobulin treatment in refractory uveitis Intravenous immunoglobulin versus corticosteroid in treatment of Graves' ophthalmopathy Randomized trial of intravenous immunoglobulins versus prednisolone in Graves' ophthalmopathy Treatment of paraneoplastic visual loss with intravenous immunoglobulin: report of 3 cases Improvement in visual fields in a patient with melanoma-associated retinopathy treated with intravenous immunoglobulin A case-bycase protocol of membranous nephropathy treatment with endovenous infusion of high doses of human immunoglobulins Intravenous immunoglobulin therapy of membranous nephropathy: efficacy and safety The short-and long-term outcomes of membranous nephropathy treated with intravenous immune globulin therapy. Kanazawa Study Group for Renal Diseases and Hypertension High-dose intravenous immunoglobulin pulse therapy in patients with progressive immunoglobulin A nephropathy: a long-term follow-up Intravenous immunoglobulin as a treatment for BK virus associated nephropathy: one-year follow-up of renal allograft recipients Intravenous immunoglobulin as rescue therapy for BK virus nephropathy Clinical efficacy of intravenous immunoglobulin for patients with MPO-ANCAassociated rapidly progressive glomerulonephritis Successful use of high dose intravenous immunoglobulin in rapidly progressive crescentic glomerulonephritis with vasculitis Treatment of antineutrophil cytoplasmic autoantibodypositive systemic vasculitis and glomerulonephritis with pooled intravenous gamma globulin Successful treatment of chronic antibody-mediated rejection with IVIG and rituximab in pediatric renal transplant recipients Early diagnosis and successful treatment of acute antibodymediated rejection of a renal transplant Plasmapheresis, intravenous cytomegalovirus-specific immunoglobulin and reversal of antibody-mediated rejection in a pediatric renal transplant recipient: a case report Posttransplant therapy using high-dose human immunoglobulin (intravenous gamma globulin) to control acute humoral rejection in renal and cardiac allograft recipients and potential mechanism of action Intravenous immunoglobulin compared with cyclophosphamide for proliferative lupus nephritis Intravenous immunoglobulin treatment of lupus nephritis Intravenous immunoglobulin therapy in a patient with lupus serositis and nephritis Successful treatment of rapidly progressive lupus nephritis associated with anti-MPO antibodies by intravenous immunoglobulins Intravenous immunoglobulin therapy in the treatment of patients with pemphigus vulgaris unresponsive to conventional immunosuppressive treatment The role of IVIG treatment in severe pemphigus vulgaris Treatment of pemphigus with intravenous immunoglobulin Corticosteroid-sparing effect of intravenous immunoglobulin therapy in patients with pemphigus vulgaris Effectiveness of intravenous immunoglobulin therapy for skin disease other than Toxic Epidermal Necrolysis: a retrospective review of Mayo Clinic experience Intravenous immunoglobulin therapy for patients with pemphigus foliaceus unresponsive to conventional treatment Influence of IVIg therapy on autoantibody titers to desmoglein 1 in patients with pemphigus foliaceus Steroid sparing effect of intravenous immunoglobulin therapy in patients with pemphigus foliaceus Intravenous immunoglobulin therapy for patients with bullous pemphigoid unresponsive to conventional immunosuppressive treatment Role of intravenous immunoglobulin in the treatment of bullous pemphigoid: analysis of current data Treatment of oral pemphigoid with intravenous immunoglobulin as monotherapy. Long-term follow-up: influence of treatment on antibody titers to human alpha6 integrin A severe persistent case of pemphigoid gestationis treated with intravenous immunoglobulin and cyclosporin Effect of high-dose intravenous immunoglobulin therapy in Stevens-Johnson syndrome: a retrospective, multicenter study Intravenous immunoglobulin therapy for children with Stevens-Johnson syndrome Prospective, noncomparative open study from Kuwait of the role of intravenous immunoglobulin in the treatment of toxic epidermal necrolysis High-dose intravenous immunoglobulin for severe drug reactions: efficacy in toxic epidermal necrolysis Intravenous immunoglobulin treatment for Stevens-Johnson syndrome and toxic epidermal necrolysis: a prospective noncomparative study showing no benefit on mortality or progression Treatment of toxic epidermal necrolysis. Experience with 9 patients with consideration of intravenous immunoglobulin Intravenous immunoglobulin for treatment of toxic epidermal necrolysis Use of intravenous immunoglobulin in children with Stevens-Johnson syndrome and toxic epidermal necrolysis: seven cases and review of the literature Treatment of toxic epidermal necrolysis with high dose intravenous immunoglobulins: multicenter retrospective analysis of 48 consecutive cases Analysis of intravenous immunoglobulin for the treatment of toxic epidermal necrolysis using SCORTEN: the University of Miami Experience Treatment of toxic epidermal necrolysis with intravenous immunoglobulin in children Intravenous immunoglobulin does not improve outcome in toxic epidermal necrolysis A randomized controlled evaluator-blinded trial of intravenous immunoglobulin in adults with severe atopic dermatitis Adjunctive high-dose intravenous immunoglobulin treatment for resistant atopic dermatitis: efficacy and effects on intracellular cytokine levels and CD4 counts The treatment of atopic dermatitis with adjunctive high dose intravenous immunoglobulin: a report of three patients and review of the literature High dose immunoglobulin in atopic dermatitis and hyper-IgE syndrome A review of high-dose intravenous immunoglobulin treatment for atopic dermatitis Intravenous immunoglobulin un autoimmune chronic urticaria The effectiveness of low dose intravenous immunoglobulin in chronic urticaria Effect of highdose intravenous immunoglobulin delayed pressure urticaria Solar urticaria: one case treated by intravenous immunoglobulin Treatment of solar urticaria by intravenous immunoglobulins and PUVA therapy Intravenous immunoglobulin therapy suppresses manifestations of the angioedema with hypereosinophilia syndrome Psoriasis: response to high-dose intravenous immunoglobulin in three patients Treatment of pyoderma gangrenosum with intravenous immunoglobulin Pyoderma gangrenosum treated with high-dose intravenous immunoglobulins: two cases and review of literature Nephrogenic fibrosing dermopathy: response to high-dose intravenous immunoglobulin Pretibial myxedema and high-dose intravenous immunoglobulin treatment Scleromyxedema. A case series highlighting long-term outcomes of treatment with intravenous immunoglobulin (IVIG) Scleromyxoedema: treatment of cutaneous and systemic manifestations with high-dose intravenous immunoglobulin Scleromyxedema: response to highdose intravenous immunoglobulin (hdIVIg) Arndt-Gottron scleromyxedema: successful therapy with intravenous immunoglobulins Combination oral prednisone and intravenous immunoglobulin in the treatment of scleromyxedema Successful therapy of scleromyxedema Arndt-Gottron with low-dose intravenous immunoglobulin Marked improvement in scleromyxedema with high-dose immunoglobulin Tumorous variant of scleromyxedema. Successful therapy with intravenous immunoglobulins Use of IGIV in the treatment of atopic dermatitis, urticaria, scleromyxedema, pyoderma gangrenosum, psoriasis, and pretibial myxedema Effect of IVIG on the hair regrowth in a common variable immune deficiency patient with alopecia universalis Regression of Kaposi's sarcoma after intravenous immunoglobulin treatment for polymyositis Efficacy and safety of intravenous immunoglobulin in patients with metastatic melanoma Intravenous immunoglobulin as prophylaxis of chemotherapy-induced oral mucositis Total remission of thymus carcinoma after treatment with intravenous immunoglobulin Thymoma and immunodeficiency (Good syndrome): a report of 2 unusual cases and review of the literature Diabetic demyelinating polyneuropathy responsive to intravenous immunoglobulin therapy Intravenous immunoglobulin therapy markedly ameliorates muscle weakness and severe pain in proximal diabetic neuropathy Simultaneous multiple cranial nerve neuropathies and intravenous immunoglobulin treatment in diabetes mellitus A case of diabetic amyotrophy with severe atrophy and weakness of shoulder girdle muscles showing good response to intravenous immune globulin Antibodymediated rejection of a pancreas allograft Multifocal motor neuropath, type 1 diabetes and asymptomatic Hashimoto's thyroiditis: an unusual association Multifocal motor neuropathy and asymptomatic Hashimoto's thyroiditis: first report of association Thyrotoxic autoimmune encephalopathy in a female patient: only partial response to typical immunosuppressant treatment and remission after thyroidectomy High dose immunoglobulin IV treatment in adrenoleukodystrophy Discussion on: high dose immunoglobulin IV treatment in adrenoleukodystrophy Waterhouse-Friderichsen syndrome and bilateral renal cortical necrosis in meningococcal sepsis Autoimmune polyendocrine syndrome. Treatment with intravenous immunoglobulins Rituximab and intravenous immunoglobulins for relapsing postinfectious opsoclonus-myoclonus syndrome Treatment of idiopathic opsoclonus-myoclonus syndrome with intravenous immunoglobulin Parainfectious opsoclonus-myoclonus syndrome: high dose intravenous immunoglobulins are effective Forty-one year follow-up of childhood-onset opsoclonus-myoclonus-ataxia: cerebellar atrophy, multiphasic relapses, and response to IVIG Treatment with intravenously administered immunoglobulins of the neuroblastoma-associated opsoclonus-myoclonus Treatment of opsoclonus-myoclonus with high-dose intravenous immunoglobulin Neuroblastoma-associated opsoclonus-myoclonus treated with intravenously administered immune globulin G High-dose i.v. human immunoglobulin in a case with infantile opsoclonus polymyoclonia syndrome Clinical outcome in adult onset idiopathic or paraneoplastic opsoclonusmyoclonus Therapeutic plasma exchange and intravenous immunoglobulin for obsessive-compulsive disorder and tic disorders in childhood Intravenous immunoglobulin in relapsingremitting multiple sclerosis: a dose-finding trial Intravenous immunoglobulin in primary and secondary chronic progressive multiple sclerosis: a randomized placebo controlled multicentre study No effect of intravenous immunoglobulins on cytokine-producing lymphocytes in secondary progressive multiple sclerosis Intravenous immunoglobulins in the treatment of relapsing remitting multiple sclerosis-results of a retrospective multicenter observational study over five years Intravenous immunoglobulin in secondary progressive multiple sclerosis: randomised placebo-controlled trial Intravenous immunoglobulin G for the treatment of relapsing-remitting multiple sclerosis: a meta-analysis Intravenous immunoglobulins in therapy of intermittent multiple sclerosis. An update Sarova-Pinhas I (1998) Intravenous immunoglobulin treatment in multiple sclerosis. Effect on relapses A double-blind, cross-over trial of intravenous immunoglobulin G in multiple sclerosis: preliminary results Immunotherapy for Guillain-Barré syndrome: a systematic review High-dose immunoglobulin therapy for Guillain-Barré syndrome in Japanese children Intravenous immune globulins in patients with Guillain-Barré syndrome and contraindications to plasma exchange: 3 days versus 6 days Intravenous immunoglobulin therapy for Guillain-Barré syndrome with IgG anti-GM1 antibody Randomised trial of plasma exchange, intravenous immunoglobulin, and combined treatments in Guillain-Barré syndrome Intravenous immune globulin in the Guillain-Barré syndrome Immunotherapy for IgM antimyelin-associated glycoprotein paraprotein-associated peripheral neuropathies A randomised controlled trial of intravenous immunoglobulin in IgM paraprotein associated demyelinating neuropathy A controlled study of intravenous immunoglobulin in demyelinating neuropathy with IgM gammopathy Intravenous immunoglobulin therapy in amyotrophic lateral sclerosis Effect of high-dose intravenous immunoglobulin on amyotrophic lateral sclerosis and multifocal motor neuropathy Effects of intravenous immunoglobulin on muscle weakness and calcium-channel autoantibodies in the Lambert-Eaton myasthenic syndrome Treatment of stiff-man syndrome with intravenous immune globulin Treatment of stiffman syndrome with intravenous immunoglobulin Long-term remission of refractory stiff-man syndrome after treatment with intravenous immunoglobulin High-dose intravenous immune globulin for stiff-person syndrome High dose immunoglobulin IV treatment in adrenoleukodystrophy Treatment of refractory epilepsy with intravenous immunoglobulins. Results of the first double-blind/ dose finding clinical study Intravenous immunoglobulin: a single-blind trial in children with Lennox-Gastaut syndrome Effects of early treatment with immunoglobulin on critical illness polyneuropathy following multiple organ failure and gramnegative sepsis Failure of high dose intravenous immunoglobulins to alter the clinical course of critical illness polyneuropathy Experience with immunomodulatory treatments in Rasmussen's encephalitis Positive response to immunomodulatory therapy in an adult patient with Rasmussen's encephalitis Improvement in adult-onset Rasmussen's encephalitis with long-term immunomodulatory therapy Medical treatment of Rasmussen's syndrome (chronic encephalitis and epilepsy): effect of high-dose steroids or immunoglobulins in 19 patients Intravenous immune globulin (10% caprylate-chromatography purified) for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (ICE study): a randomised placebocontrolled trial Randomized controlled trial of intravenous immunoglobulin versus oral prednisolone in chronic inflammatory demyelinating polyradiculoneuropathy Randomized controlled trial of IVIg in untreated chronic inflammatory demyelinating polyradiculoneuropathy Intravenous immunoglobulin treatment in chronic inflammatory demyelinating polyneuropathy. A double-blind, placebo-controlled, cross-over study Intravenous immunoglobulin for myasthenia gravis IV immunoglobulin in patients with myasthenia gravis: a randomized controlled trial Randomized, controlled trial of intravenous immunoglobulin in myasthenia gravis Immunoglobulin treatment versus plasma exchange in patients with chronic moderate to severe myasthenia gravis Immunoglobulin treatment in refractory myasthenia gravis High-dose, rapid-infusion IVIG in postvaccination acute disseminated encephalomyelitis Outcome of severe encephalomyelitis in children: effect of highdose methylprednisolone and immunoglobulins Effectiveness of intravenous immunoglobulin treatment in adult patients with steroid-resistant monophasic or recurrent acute disseminated encephalomyelitis Improvement of atypical acute disseminated encephalomyelitis with steroids and intravenous immunoglobulins Dramatic improvement of severe acute disseminated encephalomyelitis after treatment with intravenous immunoglobulin in a three-year-old boy Treatment of acute disseminated encephalomyelitis with intravenous immunoglobulin Brief report: a pilot open clinical trial of intravenous immunoglobulin in childhood autism Early and prolonged intravenous immunoglobulin replacement therapy in childhood agammaglobulinemia: a retrospective survey of 31 patients Highvs. low-dose immunoglobulin therapy in the long-term treatment of Xlinked agammaglobulinemia Efficacy of intravenous immunoglobulin on the prevention of pneumonia in patients with agammaglobulinemia Intravenous immunoglobulin therapy for antibody deficiency The effect of two different dosages of intravenous immunoglobulin on the incidence of recurrent infections in patients with primary hypogammaglobulinemia Intravenous immunoglobulin, splenectomy and antibiotic prophylaxis in Wiscott-Aldrich syndrome New diagnostic and therapeutic aspects of hyper-IgE syndrome Hyperimmunoglobulin E syndrome: two cases and a review of the literature High dose intravenous immunoglobulin in atopic dermatitis and hyper-IgE syndrome Immunodeficiency presenting as hypergammaglobulinaemia with IgG2 subclass deficiency Deficiency in immunoglobulin subclasses as cause of increased infection susceptibility-a family study Chronic rhinosinusitis and recurrent nasal polyps in two children with IgG subclass deficiency and review of the literature A case of IgG subclass deficiency with the initial presentation of transient hypogamma immunoglobulinemia of infancy and a review of IgG subclass deficiencies Antibody response in patients with osteomyelitis of the mandible. Oral Surg Oral Med Oral Pathol Oral Radiol Endod Clinical and laboratory characteristics of 75 patients with specific polysaccharide antibody deficiency syndrome Selective antibody immune deficiency in a patient with Smith-Lemli-Opitz syndrome Clinical, immunologic and genetic analysis of 29 patients with autosomal recessive hyper-IgM syndrome due to activation-induced cytidine deaminase deficiency The hyper-IgM syndrome: 13 observations Effects of intravenous immunoglobulin on clinical and immunological findings of patients with humoral immunodeficiency diseases Non-X-linked hyperimmunoglobulin M syndrome with chronic interstitial pneumonitis Successful management of neutropenia in a patient with CD40 ligand deficiency by immunoglobulin replacement therapy Hyper-IgM syndrome: report of one case Transient hypogammaglobulinemia of infancy presenting as Staphylococcus aureus sepsis with deep neck infection Transient hypogammaglobulinemia of infancy with severe bacterial infections and persistent IgA deficiency Hematopoietic stem-cell transplantation for the treatment of severe combined immunodeficiency Efficacy of intravenous immunoglobulin in the prevention of pneumonia in patients with common variable immunodeficiency