Warner, G. Scott MD, FACP, FCCP; Chaney, Kimberly L. MSN, CRNP
The assessment of acute hypercarbic respiratory failure in a previously healthy host has a broad differential diagnosis. Excluding those with intrinsic lung disease and extrinsic chest wall abnormalities, neuromuscular disease and drugs/poisons are the chief concerns. With neurological symptoms, organophosphate poisoning, botulism, and Guillain-Barré syndrome (GBS) emerge as chief considerations. Wound botulism, in particular, is often a clinical diagnosis because cultures and serology are frequently unfruitful. All forms of botulism cause progressive weakness, bulbar signs (blurred vision, diplopia, mydriasis, dysphagia, and dysarthria), and respiratory failure with normal sensation and mentation. Electrophysiological studies can help confirm botulism, especially when bioassays are negative.
A 34-year-old immunocompetent, white man presented to a local community hospital after a diving accident which resulted in a right heel wound and fracture, as well as a closed fracture of the left os calcis. This occurred as a result of diving into a shallow, freshwater riverbed, which is located several hundred yards from a commercial poultry-processing factory. He was seen and discharged from a local emergency department on the day of the injury with a stellate superficial right heel laceration. He was scheduled for outpatient orthopedic evaluation, which he did not keep. The patient did not receive antibiotics or tetanus toxoid. The wound was not irrigated and did not require sutures.
For the following 10 days, he noticed a purulent drainage from the wound of the right heel. Gradually, he began to have dysarthria, dysphonia, difficulty swallowing, coughing during meals, double vision, and fever. He presented to our Regional Medical Center for evaluation, at which time dysarthria, mydriasis, and ptosis were noted. He displayed no excessive lacrimation or bronchorrhea. He had no rash. Sensation and mental status were intact. Vital signs were normal except for temperature of 39°C. Results of the urine drug screens and human immunodeficiency virus titer were normal. Blood count showed a mildly elevated white blood cell count of 13,000/mm3. No tetany or fasciculations were noted. Computed tomography of the brain was normal. A lumbar puncture was performed in the emergency department to evaluate the possibility of GBS-especially the descending Miller Fisher variant, Lyme disease, West Nile virus, meningitis, and others. Results of the cerebrospinal fluid showed no cells, negative stains, and normal protein and glucose.
The initial physical examination revealed significant cranial nerve abnormalities, particularly mydriasis, ptosis, and inability to abduct the eyes. Deep tendon reflexes were spared. Chief among the differential diagnoses was botulism and other neurotoxic pathologies. Results of the lumbar puncture, electromyography (EMG), and deep tendon reflexes upon examination helped differentiate this case from GBS, which was the primary differential diagnosis. There were no recent exposures to implicate envenomation, poisoning, or ingestion. No other household contacts eating the same diet became ill. Laryngoscopy was performed, confirming aspiration of saliva and ineffective cough. Serial bedside spirometry confirmed worsening respiratory failure. Oximetry later showed hypoxemia requiring supplemental oxygen.
The patient was transferred into the critical care unit on hospital day 2 and begun on high doses of intravenous penicillin G. The clinical diagnosis of botulism was supported with EMG with repetitive muscle stimulation at 20 to 50 Hz, which showed augmentation of potentials seen in botulism and Eaton-Lambert syndrome. Brief synaptic abundant potentials and compound muscle action potentials were consistent with the clinical diagnosis of botulism. No abnormal f waves typical of GBS were seen. The Centers for Disease Control and Prevention (CDC) was contacted to release botulism antitoxin. The botulinum equine trivalent antitoxin was delivered and administered within 12 hours upon request. The patient was taken to the operating room where wound debridement was performed on the right heel. Cultures revealed methicillin-resistant Staphylococcus epidermidis, Enterococcus faecalis, and Stenotrophomonas maltophilia. The anaerobic cultures did not reveal any clostridia.
The patient displayed signs of respiratory muscle fatigue and developed significant respiratory acidosis and relative hypoxemia. Initially, he was placed on noninvasive, positive pressure ventilation for 24 hours; however, despite maximal pressure delivery, he improved but continued to have some uncorrected respiratory acidosis and was unable to protect his airway because of bulbar paresis. It was at this time that he was endotracheally intubated and maintained on mechanical ventilation. A second surgical debridement of the right heel wound to include repeat soft tissue and bone cultures was performed on hospital day number 5. Blood, urine, cerebrospinal fluid, and the second wound culture were all sterile. Serum botulinum toxin levels were negative. The wound was not tested for botulism by mouse bioassay or polymerase chain reaction.
Slowly, the respiratory insufficiency and neurological deficits, particularly ptosis and ocular paresis, improved for the next 2 weeks. He was successfully extubated on hospital day 13. Broad-spectrum antibiotics were administered to target all bacteria identified in the heel wound, in addition to high-dose intravenous penicillin G for botulism. In addition to the above findings, the patient also had severe constipation and needed parenteral nutrition administered for the first week of his hospital stay.
Clostridium botulinum is an anaerobic bacterium commonly found in soil. The bacteria form spores, which allow them to survive in a dormant state until exposed to conditions that can support their growth. In the United States, the CDC documents an average of 110 cases of botulism that are reported each year. Of these, approximately 25% are food borne, 72% are infant botulism, and the rest are wound botulism. Outbreaks of food-borne botulism involving 2 or more persons occur in most years and are usually caused by eating contaminated home-canned foods. Wound botulism is a rare complication of Clostridium infections. It was not until the first half of the 20th century that wound botulism was discovered.1 The number of cases of food-borne and infant botulism has changed little in recent years, but wound botulism has increased because of the use of black tar heroin, especially in California. The diagnosis may be extremely difficult to make. All forms of botulism cause progressive weakness, bulbar signs (blurred vision, diplopia, mydriasis, dysphagia, and dysarthria), and respiratory failure with normal sensation and mentation. Treatment is aimed at the following: maintaining respiration via intubation and mechanical ventilation, stopping progression of weakness by administration of botulism antitoxin (equine trivalent botulinum antitoxin for adults and botulism immune globulin intravenous [human] for infant botulism), and preventing complications from weeks of paralysis with good supportive care. Attention to eye care is crucial because these patients have increased risk for corneal desiccation because of inadequate lubrication and blinking. The source of botulinum toxin should be identified to prevent additional cases.2 The mortality rate is approximately 5% with support. The EMG does help distinguish this from myasthenia gravis in that the evoked potentials increase with subsequent stimulation, similar to the Eaton-Lambert syndrome.
This case underscores a classic presentation of botulism and the need to maintain a high index of suspicion for probable wound botulism, which often is not confirmed with microbiological cultures or serology. Serum toxin by polymerase chain reaction is detectable in less than 20% of cases reported. The mouse bioassay is a much more useful test and allows toxin typing by the use of type-specific botulinum antitoxins. There are 7 types of botulism toxin designated by the letters A to G; only types A, B, E, and F cause illness in humans. The toxin acts by blocking the release of acetylcholine at the neuromuscular junction in a dose-dependent fashion.3 It is notable as well that most cases and case reports of botulism are food borne. The remaining recent literature involve case reports of wound botulism occurring in injection drug users.4-6 This case highlights another, albeit rare, source of wound botulism occurring in association with a polymicrobial wound infection with several fecal pathogens occurring presumably from contaminated fresh water. Certainly, he could have gotten botulism from food or from poor wound care after the injury, but these are considered less likely. Electrophysiological studies can help confirm botulism, especially when bioassays are negative. The typical finding is that of small evoked muscle action potentials in response to a single supramaximal nerve stimulus in a clinically effected muscle.7 Antitoxin does not reverse the paralysis but generally slows or halts further progression of paralysis if administered early.
Medical care providers who suspect a diagnosis of botulism in a patient should immediately call their state health department's emergency 24-hour telephone number. The state health department will contact CDC to arrange for a clinical consultation by telephone and, if indicated, release of botulinum antitoxin.
State health departments should call 770-488-7100-the CDC's 24-hour telephone number-to report suspected botulism cases, obtain clinical consultation on botulism cases, and request botulinum antitoxin release. The call will be taken by the CDC Emergency Operations Center, which will page the Foodborne and Diarrheal Diseases Branch medical officer on call. The 1996-revised CDC case definition of botulism8 is as follows:
* Clinical description. Common symptoms are diplopia, blurred vision, and bulbar weakness. Symmetric paralysis may progress rapidly. Food-borne ingestion of botulinum toxin results in an illness of variable severity. Wound botulism is an illness resulting from toxin produced by C.botulinum that has infected a wound.
* Case classification. Probable: a clinically compatible case with an epidemiological link (eg, ingestion of a home-canned food within the previous 48 hours). Confirmed: a clinically compatible case that is laboratory confirmed or that occurs among persons who ate the same food as persons who have laboratory-confirmed botulism, a clinically compatible case that is laboratory confirmed in a patient who has no suspected exposure to contaminated food and who has a history of a fresh contaminated wound during the 2 weeks before onset of symptoms, or a clinically compatible case that is laboratory confirmed in a patient aged 1 year or older who has no history of ingestion of suspect food and has no wounds. Laboratory criteria for diagnosis: detection of botulinum toxin in serum, stool, or patient's food or isolation of C. botulinum from stool or wound.
Hypercarbic respiratory failure with oculoparesis is a typical manifestation of botulism. Most cases of botulism are food borne. Wound botulism comprises 3% of reported cases with most occurring in injection drug users. This case highlights another probable, albeit rare, source of wound botulism occurring in association with a polymicrobial wound infection with several fecal pathogens occurring presumably from contaminated freshwater. The difficulty in obtaining laboratory confirmation, particularly in wound botulism, is illustrated. Increased awareness of botulism as a potential agent of biological terrorism will also raise awareness of the disease and improve early detection of naturally occurring cases of botulism. Early suspicion and thus earlier administration of antitoxin will likely improve outcomes by slowing disease progression.
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5. Passaro DJ, Werner SB, McGee J, et al. Wound botulism associated with black tar heroin among injecting drug users. JAMA. 1998;279:859-863.
6. Merrison AFA, Chidley KE, Dunnett J, et al. Wound botulism associated with subcutaneous drug use. BMJ. 2002;325:1020-1021.
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8. CDC. Botulism case definitions. MMWR Morb Mortal Wkly Rep. 1997;46:1-55.
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