Introduction

Botulinum toxins are used to treat a large number of muscle hyperactivity disorders, including dystonia, spasticity, and tremor, autonomic disorders, such as hyperhidrosis and hypersalivation, as well as facial wrinkles. Commercially available products differ with respect to serotype, formulation, and purity. Not all products are approved in all countries. Serotype A-containing products are Botox®, Dysport®, Chinese BoNT-A (CBTX-A) and Xeomin®, whereas NeuroBloc®/Myobloc® contains serotype B. The active ingredient in all products is botulinum neurotoxin (BoNT), a di-chain protein with a molecular weight of 150 kDa. Botulinum toxin type A (BoNT-A) inhibits release of acetylcholine by cleaving the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein SNAP 25 while BoNT type B (BoNT-B) cleaves vesicle-associated membrane protein (VAMP) II. Since BoNTs are foreign proteins, the human immune system may respond to them with the production of specific anti-BoNT antibodies (BoNT-AB). The probability of developing BoNT-AB increases with the BoNT doses applied (Göschel et al., 1997). Whether other drug-related factors might contribute to immune responses is discussed below. Patient-related factors may also be involved in triggering BoNT-AB formation. Recently, a patient was reported who was treated with Dysport for several years with good results until he developed BoNT-AB-induced therapy failure after he received BoNT following a wasp sting (Paus et al., 2006). Since components of wasp poison are effective immunostimulants, a preactivation of lymphocytes may have triggered BoNT-A-AB formation.