Clinical Mimics of Infant Botulism

Since 1992, Human Botulism Immune Globulin has been provided by the California Department of Health Services to infants with probable infant botulism, the intestinal toxemia form of human botulism. Human Botulism Immune Globulin became available in California in 1992–1997 within a randomized, controlled, double-blinded, pivotal clinical trial and subsequently became available nationwide in 1998–2003 in an open-label study until its licensure in October 2003 as BabyBIG. Thereafter, Human Botulism Immune Globulin remained available nationwide as an approved orphan-drug product. To achieve prompt neutralization of circulating botulinum toxin, the decision to treat with Human Botulism Immune Globulin has been based on clinical criteria that include a consistent history and physical findings of bulbar palsies, hypotonia, and weakness. After licensure, the charts of patients who did not have laboratory-confirmed infant botulism were reviewed to identify their actual diagnoses. The 5% of 681 patients treated with Human Botulism Immune Globulin who did not have infant botulism fell into 5 categories: spinal muscular atrophy, metabolic disorders, other infectious diseases, miscellaneous, and probable infant botulism lacking laboratory confirmation. INFANT BOTULISM IS the infectious intestinal toxemia form of human botulism that results when ingested spores of Clostridium botulinum (or, rarely, neurotoxigenic Clostridium butyricum or Clostridium baratii) colonize the large intestine and then produce botulinum toxin in its lumen.1,2 Botulinum toxin blocks the release of acetylcholine at the neuromuscular junction and other peripheral cholinergic synapses, which results in constipation, lethargy, poor feeding, generalized weakness, decreased head control, hypotonia, diminished deeptendon reflexes, hypoventilation, and cranial nerve palsies. Symmetrical bulbar nerve palsies (eg, ptosis, sluggish pupillary response to light, ophthalmoplegia, poor suck, decreased gag reflex, difficulty swallowing, expressionless face) are cardinal features of infant botulism that help distinguish it from other causes of subacuteto acute-onset generalized weakness. After an 15-year development period that included 2 clinical trials,3 the US Food and Drug Administration licensed Botulism Immune Globulin Intravenous (Human) (BIG-IV) as BabyBIG to the California Department of Health Services (CDHS) in October 2003. Because BIG-IV is the only specific treatment for infant botulism, it became the standard of care for infants who presented with the clinical picture of infant botulism. Treatment with BIG-IV should be given as early as possible in the illness to neutralize botulinum toxemia and thereby shorten hospital stay maximally.3,4 Approximately 5% of the 681 patients since 1992 who were treated with BIG-IV (or placebo during the randomized, controlled clinical trial3) were found not to have infant botulism, and in most of these cases an alternative diagnosis was established. The tabulation of those conditions that so closely mimicked infant botulism that the attending physicians and the consulting