Botulism (ORPHA:1267)
Botulism is a rare acquired neuromuscular junction disease, characterized by descending flaccid paralysis caused by botulinum neurotoxins (BoNTs), including four clinical forms with different modes of acquisition.
Epidemiology
Estimated global prevalence is less than 1/1,000,000. Annual incidence in Western countries is estimated at 1/2,000,000.
Clinical description
The incubation period usually lasts 12 to 36 h, sometimes up to 5-8 days depending on the disease form. The typical clinical picture includes symmetrical cranial nerve palsies followed by symmetrical descending flaccid motor paralysis, with cholinergic dysautonomia. Initial symptoms include blurry vision (accommodation defects, diplopia) with bilateral ptosis, followed by dysautonomic symptoms (dry mouth and eyes, mydriasis, dysphagia, dysarthria, urinary retention and constipation). In the severe forms, paralysis concerns the neck, shoulder, and proximal muscles, followed by involvement of the muscles of the distal upper extremities, the diaphragm and respiratory muscles, which may result in respiratory compromise or arrest. The sensory system and intellectual functions remain unaffected.
Etiology
Clinical manifestations are common to all forms, whatever the mode of acquisition. Foodborne botulism (see this term) caused by consumption of foods contaminated with BoNTs (homemade or traditional canned-foods, ham, pork products, etc) is the most frequent form of botulism in adults. Intestinal colonization by Clostridium botulinum and in situ toxin production is observed in young infants (infant botulism) and certain adults with risk factors (adult intestinal botulism; see these terms). Wound (or inoculation) botulism, through infection of wounds, is rare and mainly occurs in injection drug users; inhalational botulism and iatrogenic botulism have also been reported (see these terms). Botulism is due to BoNTs produced by C. botulinum and, very rarely, by certain related Clostridia, rod-shaped, strictly anaerobic and sporulating bacteria, i.e neurotoxigenic strains of C. baratii and C. butyricum. There are seven types of BoNTs (A to G) with different antigenic properties. Types A, B, E and, more rarely F, are associated with human botulism. At the site of absorption or adsorption, BoNT diffuses via the blood to the presynaptic membrane of skeletal and autonomic cholinergic nerves. BoNT binds to and enters peripheral cholinergic terminals and causes a block of acetylcholine release, with ensuing flaccid paralysis.
Diagnostic methods
Diagnosis is essentially clinical in the first stage; the electromyography (EMG) pattern is characterized by brief, small, abundant potentials (BSAPs). Confirmation is based on BoNT detection in serum, stools, and/or food samples. The detection of BoNT-producing Clostridium in cultures from stools and food or wound samples also supports the diagnosis.
Differential diagnosis
Differential diagnosis, depending on the disease form, in adults or infants, includes myasthenia, Guillain-Barré syndrome (and Miller Fisher syndrome), Lambert-Eaton syndrome (see these terms), bacterial and chemical food poisoning or chemical intoxication.
Management and treatment
Treatment is symptomatic. Management is based on supportive care and respiratory assistance with recovery in severe cases, in an intensive care unit (ICU). Anti-toxin therapy is effective when it is administrated at the onset of symptoms. In Europe, the formulation currently available for adults is trivalent (anti-A, B, E). A heptavalent (anti-A to G) product is also available. In the USA, bivalent (anti A, B) and monovalent (anti-E) antitoxins are distributed; for infant botulism, a human derived botulinum immune globulin (BIG-IV, anti-A-B) is available.
Prognosis
Prognosis varies depending on the different forms of botulism, but is generally correlated with the rapidity of diagnosis and medical assistance. Death resulting from respiratory failure is rare when the patients receive appropriate medical assistance.

                            Last update: 
                            January 2011


                            - Expert reviewer(s): 
                            Dr Michel POPOFF