Iatrogenic botulism: a risk for botulinum toxin's medical use?
摘要
Botulinum toxin (BT) is infamous for its extreme toxicity. If it enters the bloodstream, it can cause botulism presenting with a typical pattern of motor and autonomic dysfunction. An international expert panel organised by IAB—Interdisciplinary Working Group for Movement Disorders explored iatrogenic botulism after BT's medical use (IB), reached conclusions and formulated recommendations. When injected into its target tissue, BT binds to gangliosides on cholinergic nerve terminals before it is internalised permanently. Small amounts of BT, however, are circulating within the bloodstream. When BT type B is applied, IB-B occurs frequently, typically affecting the autonomic nervous system. When BT type A is applied, IB-A only occurs in special circumstances, even when high doses are used. We identified 236 patients with IB-A in the literature. All IB-A was mild or moderate and fully reversible. In 212 patients, it occurred with unapproved BT use. In 116 of them, unapproved BT preparations were used, in 81, unapproved indications were treated and in 15, underlying neuromuscular impairment including myasthenia gravis, Lambert-Eaton myasthenic syndrome, amyotrophic lateral sclerosis and spinal muscle atrophy were contraindications for BT use. In 24 patients, IB-A occurred in approved BT use. Their evaluation was frequently incomplete, so that causes for IB-A often remain unclear. They may include presence of differential diagnosis, subclinical neuromuscular impairment and interference with additional diseases. When IB is suspected, proper evaluation is necessary to verify it and to identify its causes. Off-label use is common in BT therapy. However, it should be performed with caution, especially in children and when high doses are applied. High BT doses should not be applied to low volumes of target tissues, in order not to exceed the BT binding capacity.