Intramuscular immunoglobulin (IMIg) therapy was limited by frequent reactions and painful administration

Intramuscular immunoglobulin (IMIg) therapy was limited by frequent reactions and painful administration. to pain and swelling at the infusion site, and one paused therapy following post-infusion migraines. Ultrasound imaging of paired conventional and facilitated SCIg demonstrated clear differences in subcutaneous space distribution associated with a 10-fold increase in rate and volume delivery with fSCIg. Patient profiles for those choosing fSCIg fell into two main categories: those experiencing clinical problems with their current treatment and those seeking greater convenience and flexibility. When introducing fSCIg, consideration of the type and programming of infusion pump, needle BEC HCl gauge and length, infusion site, up-dosing schedule, home training and patient information are important, as these may differ from conventional SCIg. This paper provides guidance on practical aspects of the administration, training and outcomes to help inform decision-making for this new treatment modality. Keywords:facilitated subcutaneous immunoglobulin (fSCIg), hyaluronidase, intravenous immunoglobulin (IVIg), primary immunodeficiency (PID), subcutaneous immunoglobulin (SCIg) == Introduction == Immunoglobulin (Ig) G replacement therapy is the cornerstone of treatment for primary and most secondary antibody deficiencies and acts to prevent serious infection1. Replacement is lifelong, thus acceptability and ease of administration are vital for adherence to treatment. The introduction of Ig replacement therapy for a boy with agammaglobulinaemia by Bruton in 19522was remarkable for the pioneering use of subcutaneous immunoglobulin (SCIg, 32 g in 20 BEC HCl ml given weekly). A further precedent was set 10 years later with the description of hyaluronidase-facilitated intramuscular immunoglobulin, comprising 1 ml of tetracaine hydrochloride with 150 units of hyaluronidase preceding each 30 ml injection of immunoglobulin into the buttocks3. Different routes of administration followed these seminal Rabbit polyclonal to IL1R2 papers by Bruton. Intramuscular immunoglobulin (IMIg) therapy was limited by frequent reactions and painful administration. Improved manufacturing and IgG stabilizing techniques led to the use of intravenous immunoglobulin (IVIg) products, allowing administration of BEC HCl greater volumes and maintenance of physiological immunoglobulin levels at doses of approximately 04 g/kg/month. Following the development of portable syringe drivers and stabilization techniques enabling products to be formulated and administered at higher concentrations, SCIg became increasingly popular using a variety of regimens, including weekly, bi-weekly and rapid BEC HCl push4. The introduction of recombinant hyaluronidase-facilitated subcutaneous immunoglobulin (fSCIg) has brought the options in therapy almost full circle. Bruton would not have known that the efficacy of hyaluronidase in reducing resistance to bulk fluid flow would have BEC HCl been even greater if used subcutaneously, where greater amounts of its substrate hyaluronan are found compared to muscle. == Mechanism of action == Following a subcutaneous (s.c.) depot injection, a drug must pass through the skin extracellular matrix (ECM) in order to access either capillaries or the lymphatics to enter the vascular space. For small molecules, entry is via the capillaries; larger molecules such as antibodies pass into the lymphatics through their fenestrated endothelium5. The ECM contains the structural macromolecules collagen and elastin, which support cellular, vascular and lymphatic components, and all these are embedded in a viscoelastic gel made from glycosaminoglycans and proteoglycans. It is the ability of the complex polysaccharide structure of glycosaminoglycans to retain water which forms the gel-like substance, and this acts to impede the flow of fluids through the ECM. All the glycosaminoglycans except for hyaluronan are bound covalently to core proteins and are termed proteoglycans. The physiological functions of hyaluronan include lubrication (particularly in the synovium), water homeostasis, maintenance of tissue architecture and macromolecular filtering and exclusion6. It is estimated that 30% of the body’s hyaluronan is turned over per day and that the dermal barrier following administration of hyaluronidase is reconstituted within 2448 h7, in contrast to the 15-year half-life of collagen8. It is interesting to note that when hyaluronan is used in the context of cosmetic dermal fillers it needs to be treated chemically to cross-link the molecules in order to avoid rapid degradation9. The administration of hyaluronidase to break down hyaluronan temporarily and locally allows increased movement of fluid through the ECM and permits.