Generalized botulism: diagnostic problems in a patient treated with botulinum toxin type A

Abstract

Editor, Botulinum toxin type A (BT/A) is commonly used nowadays in the treatment of patients with localized muscle spasticity. The toxin is considered to be effective and safe in therapeutic doses, but cases of generalized botulism have been described, including the occurrence of a botulism-like syndrome after intramuscular injections of BT/A (Bakheit et al. 1997; Pang & O'Day 2006). Botulinum toxin is the most effective method of treatment for patients with localized muscle spasticity and can restore function sufficiently to allow patients to resume normal life. We present the case of a 67-year-old woman treated with BT/A for blepharospasm. On 26 July 2002 the patient received an injection of 125 units (1LD50) of BT/A (Dysport Clostridium; IPSEN Biopharm Ltd, ) from a 500-unit vial, administered to the orbicularis oculi muscle in the left eye. On 4 August the subject experienced nausea, vomiting, general weakness, xerostomia and hoarseness. The following day she experienced disturbances in her vision, photophobia, bilateral weakness of visual acuity and diplopia, followed later by abdominal meteorism and obstinate constipation. She also experienced problems in swallowing and disturbances in respiration. On 7 August 2002 the patient was admitted to the Department of Neurology, Medical University of Lublin. During physical examination the patient was conscious, sleepy and apathetic. Her body temperature was 36.7 °, blood pressure 95/65 mmHg and pulse 84 beats/min. During examination, the patient appeared pale and expressionless. Mydriasis, asymmetric pupils, no pupillary reaction to light, accommodation disturbances and impaired ocular movement with bilateral ptosis, especially on the left, were noted. Lack of palatine reflexes was also observed, along with xerostomia and shallow respiration with limited movement of the chest and diaphragm. The patient's breathing frequency was 24 breaths/min. Her heart rate was rhythmic, but the cardiac sound was dull. Moreover, a distended belly, suppression of peristaltic movement, full urinary bladder and lack of diuresis were observed. Muscle power in the limbs was preserved, along with hypotonicity and weakened reflexes. On the basis of this clinical picture, botulism was diagnosed. Blood tests to identify the presence of botulinum toxin were performed to confirm the diagnosis. Clinical improvement was achieved after administration of 150 ml botulinum antitoxin (polyvalent equine serum ABE composed of antitoxin botulinum A [5000 I.U.], antitoxin botulinum B [5000 I.U.] and antitoxin botulinum E [1000 I.U.] in a 10-ml vial). In laboratory diagnostics, during biological tests on mice with antitoxin neutralization, botulinum toxin type B was found to be present, which excluded BT/A Dysport as the cause of intoxication. On 16 August 2002, the 71-year-old sister of the patient was admitted to the Department of Infectious Diseases. She showed typical clinical symptoms of botulism, including symmetrical descending flaccid paralysis with prominent diplopia, dysarthria, dysphonia and dysphagia. Her initial symptoms, including xerostomia and signs of dyspepsia, had appeared 7 days after she had consumed home-preserved meat. Subsequently, it transpired that both sisters had eaten the preserved meat. In the second sister's case, biological tests on mice also confirmed the presence of botulinum toxin type B. Initial symptoms of botulinum intoxication usually appear within a time period ranging from 6 hours to 8 days; incubation time has been shown to correlate with the severity of the clinical course (Hughes et al. 1981; Cherington 1998; Shapiro et al. 1998). In the first case described here, the incubation period was short (10 hours), but in the patient's sister it was 7 days and thus it was impossible to exclude intoxication by the type A toxin after injection of BT/A. Cases of generalized botulism after BT/A have been described in the literature but after higher doses of 250–500 units (Bakheit et al. 1997). Nevertheless, the cardinal cause of botulism is the consumption of food infected with botulinum toxin. In the USA 50% of food botulism cases are caused by toxin type A, 25% by toxin type B, and the remaining cases by toxin type E (Shapiro et al. 1998). In Poland, where the most frequent cause of botulism is toxin type B, an average of 82 cases of illness have been noted per year since 1998, which is the highest in the EU (Therre 1999).