European consensus proposal for immunoglobulin therapies.

The use of immunoglobulin (Ig) preparations (intravenous, IVIg, subcutaneous, SCIg) for replacement and immunomodulation therapy worldwide has tripled in the past 20 years and represents an ever-increasing cost factor for healthcare organizations. The limited access to the starting material of this essential medicinal product is currently the driving force for human plasma collection. Increasing awareness and improved diagnosis of human primary immunodeficiencies and a broadening of immunomodulatory indications are responsible for this development, and on a longer run might lead to plasma supply shortages. Consensus recommendations for the optimal use of Ig in clinical practice, including priority rankings for the most urgent indications, are therefore urgently needed. During a recent meeting in Kreuth, Germany, expert nominees from 36 Council of Europe states, together with colleagues from observer countries and regulatory agencies came up with this consensus statement.

Is dosing of therapeutic immunoglobulins optimal? A review of a three-decade long debate in europe.

The consumption of immunoglobulins (Ig) is increasing due to better recognition of antibody deficiencies, an aging population, and new indications. This review aims to examine the various dosing regimens and research developments in the established and in some of the relevant off-label indications in Europe. The background to the current regulatory settings in Europe is provided as a backdrop for the latest developments in primary and secondary immunodeficiencies and in immunomodulatory indications. In these heterogeneous areas, clinical trials encompassing different routes of administration, varying intervals, and infusion rates are paving the way toward more individualized therapy regimens. In primary antibody deficiencies, adjustments in dosing and intervals will depend on the clinical presentation, effective IgG trough levels and IgG metabolism. Ideally, individual pharmacokinetic profiles in conjunction with the clinical phenotype could lead to highly tailored treatment. In practice, incremental dosage increases are necessary to titrate the optimal dose for more severely ill patients. Higher intravenous doses in these patients also have beneficial immunomodulatory effects beyond mere IgG replacement. Better understanding of the pharmacokinetics of Ig therapy is leading to a move away from simplistic "per kg" dosing. Defective antibody production is common in many secondary immunodeficiencies irrespective of whether the causative factor was lymphoid malignancies (established indications), certain autoimmune disorders, immunosuppressive agents, or biologics. This antibody failure, as shown by test immunization, may be amenable to treatment with replacement Ig therapy. In certain immunomodulatory settings [e.g., idiopathic thrombocytopenic purpura (ITP)], selection of patients for Ig therapy may be enhanced by relevant biomarkers in order to exclude non-responders and thus obtain higher response rates. In this review, the developments in dosing of therapeutic immunoglobulins have been limited to high and some medium priority indications such as ITP, Kawasaki' disease, Guillain-Barré syndrome, chronic inflammatory demyelinating polyradiculoneuropathy, myasthenia gravis, multifocal motor neuropathy, fetal alloimmune thrombocytopenia, fetal hemolytic anemia, and dermatological diseases.

Lichen planus in a case of Good's syndrome (thymoma and immunodeficiency).

Patients with thymoma are mostly investigated for autoimmunity but a few patients may have underlying immunodeficiency that is referred to as Good's syndrome (GS). Cardiothoracic surgeons must always consider this diagnosis when undertaking thymectomy, as immunoglobulin levels can be easily measured and is readily available. The immunodeficiency in GS can be life-threatening and more importantly, it is not reversed by thymectomy. Collaborative care with an Immunologist for these patients is strongly recommended.

Therapeutic strategies in common variable immunodeficiency.

The treatment of common variable immunodeficiency (CVID) is currently based on the early recognition of the condition and replacement immunoglobulin combined with prompt treatment of infections and complications. The route of administration, dose and frequency of administration of immunoglobulin still vary between centres and countries. Other interventions aimed at overcoming the immunological defects in CVID such as interleukin-2 therapy are being studied but there is as yet insufficient evidence to support their routine use. The treatment of complications such as suppurative lung disease uses principles broadly similar to those used for cystic fibrosis, whereas the granulomatous complications involving the lungs and other organ systems are in need of much more research to define optimum therapies.