title: Diagnostic algorithm and management of immune-mediated complications associated with subcutaneous insulin therapy.
abstract: Immune mediated complications associated with subcutaneous insulin therapy such as insulin neutralizing antibodies and/or skin reactions are rare conditions since human insulin is in general use. Nevertheless, if it occurs, a stepwise diagnostic approach is essential for differential diagnosis and consecutive treatment of these complications. Here we suggest a diagnostic algorithm to deal with e.g. insulin antibody formation of the IgG and/or IgE type and/or severe skin reactions resulting in poor metabolic control and often "brittle diabetes" in affected patients. This diagnostic algorithm includes step 1: Intradermal skin testing with positive and negative controls, additives and different insulin preparations; step 2: Quantification of insulin specific IgG and IgE in the serum, and step 3: Analysis of the time dependent binding/dissociation curves of the insulin neutralizing antibodies in an ex vivo/in vitro assay to assess the clinical significance of these antibodies. Based on 158 insulin treated control subjects and four patients with typical symptoms and signs representing the spectrum of immune-mediated complications subsequent to subcutaneous insulin therapy we demonstrate that the proposed stepwise approach leads to a definite diagnosis as a prerequisite for individual and successful therapy.
authors.affiliation: Third Medical Department and Policlinic, Justus-Liebig University of Giessen, Germany. clemens.jaeger@innere.med.uni-giessen.de
authors.forename: C
authors.initials: C
authors.lastname: Jaeger
authors.forename: M
authors.initials: M
authors.lastname: Eckhard
authors.forename: M D
authors.initials: MD
authors.lastname: Brendel
authors.forename: R G
authors.initials: RG
authors.lastname: Bretzel
mesh_terms: D000328:Adult; D000465:Algorithms; D001323:Autoantibodies / Q000097:blood; D016022:Case-Control Studies; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000276:immunology; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000276:immunology*; D007073:Immunoglobulin E / Q000097:blood*; D007074:Immunoglobulin G / Q000097:blood*; D007158:Immunologic Techniques; D007279:Injections, Subcutaneous; D007328:Insulin / Q000009:adverse effects / Q000276:immunology*; D007330:Insulin Antibodies / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012882:Skin Tests
chemical_list: D001323:Autoantibodies; D007004:Hypoglycemic Agents; D007074:Immunoglobulin G; D007328:Insulin; D007330:Insulin Antibodies; D007073:Immunoglobulin E