Wound botulism presenting as dysphagia to an ENT ward

Abstract

A 44-year-old man with a background of heroin injection drug use was referred to the ear, nose and throat team with a sore throat and dysphagia. He was treated with intravenous antibiotics and steroids for suspected uvulitis. He developed progressive bulbar weakness and symmetrical descending weakness of the upper extremities over a 12-hour period and was intubated prior to transfer to the intensive care unit.

Botulinum heptavalent antitoxin was administered, and subsequent PCR assay confirmed Clostridium botulinum neurotoxin B from his most recent injection site. He was found unconscious on the ward 3 days following extubation. Postmortem confirmed he died from heroin intoxication.

This case highlights the importance of considering wound botulism in injection drug users presenting with unexplained weakness, particularly of the lower cranial nerves. Botulism is not characteristically associated with signs of localised or systemic infection in contrary to other bacterial complications of injection drug use.

Background

Clostridium botulinum is a sporing, anaerobic gram-positive bacterium which produces seven distinct neurotoxins (A to G) that irreversibly bind to receptors in the presynaptic membrane in the neuromuscular junction to block the release of acetylcholine.¹ Of the seven serotypes identified, neurotoxins A, B, E and F result in human disease. The resulting clinical syndrome is typically characterised by bilateral cranial nerve palsy and descending symmetrical flaccid paralysis. In severe cases, extensive respiratory muscle paralysis leads to ventilatory failure and death unless supportive care is provided.²

Wound botulism occurs when the botulinum spores contaminate recreational injectable drugs or drug injecting equipment, resulting in the direct inoculation of open wounds. The incidence of botulinum toxicity has increased rapidly among persons who inject drugs (PWID),³ however, it may be misdiagnosed or only recognised at a later stage. We report a case of a PWID with botulinum toxicity who was initially referred to the ear, nose and throat (ENT) team with dysphagia.

Case presentation

A 44-year-old man presented to the emergency department at a University Teaching Hospital with a 2-day history of a sore throat, difficulty swallowing and reduced oral intake. He had a background of chaotic heroin and cocaine injection drug use and street benzodiazepine use. Injection drug use was complicated by intermittent claudication due to femoral artery stenosis and chronic hepatitis C infection. There was a history of poor attendance at hospital appointments. He had last injected heroin into his left groin 4 days prior to admission. On examination, he was apyrexial and there were no signs of a systemic inflammatory response or sepsis. There was an injection sinus in the left groin which was moist but with no erythema or tenderness. Examination of the oropharynx demonstrated a swollen uvula and erythematous pharynx. There was no evidence of any oral candida or ulceration. He was referred to ENT team and treated as a suspected uvulitis with intravenous dexamethasone, intravenous benzylpenicillin and intravenous fluids.

Progressive bulbar weakness including ptosis, diplopia, blurred vision, dysphagia and dysarthria was observed over a 12-hour period from admission, approximately 4–5 days following his last heroin injection. He was also noted to have symmetrical descending weakness of the upper extremities with no sensory deficit.

The patient deteriorated rapidly with increased respiratory effort, reduced oxygen saturation and minimal facial movements. He was intubated on the ward prior to transfer to the intensive care unit (ICU). Intravenous benzylpenicillin and metronidazole were commenced, and botulinum heptavalent antitoxin was administered due to suspicion of injection-related botulism. HIV testing was negative. CT angiogram of the left groin injection site demonstrated the presence of a chronic pseudoaneurysm sac, occluded left common femoral artery and sinus tract with a possible small abscess (13 mm) medial to the tract with no evidence of any significant collection. The injection site and scan were both reviewed by the surgical team. A small amount of pus was extruded, but it felt that formal debridement was not indicated, and the risks of untargeted surgical exploration of the inguinal area were considered high given the patient’s prior vascular morbidity. The patient was also reviewed by the neurology team; however, it was felt that the clinical probability of other neurological conditions such as the Miller Fisher variant of Guillain-Barre syndrome was low in the context of his recent injection drug use, and wound botulism remained the most likely diagnosis.

Public health was notified and. C. botulinum neurotoxin type B gene was subsequently detected by PCR assay from both the left groin swab and pus culture, confirming the clinical diagnosis of botulism. There was no growth in either aerobic or anaerobic blood culture bottles.

Outcome and follow-up

The patient received intravenous antibiotics for 10 days and was ventilated for 8 days in total. He was assessed by the speech and language team while in ICU and was able to eat and drink normally. His respiratory function gradually improved with resolution of upper limb weakness and ptosis. The wound appeared to be healing well, and there was no evidence of residual infection requiring any additional treatment. No follow-up imaging was performed. The patient received dihydrocodeine as opiate replacement therapy following review by addiction specialists.

Three days following extubation and 4 hours after his last review when the patient was noted to be well and observations within normal range, he was found unrousable, pulseless and asystolic. Cardiopulmonary resuscitation was unsuccessful. Heroin was later found following a search of his clothing and opiate overdose was therefore suspected. This was confirmed on subsequent postmortem when a recent injection site was identified in his lower leg and high concentrations of morphine were detected in blood and urine.

Discussion

The UK has seen an emergence of illness caused by the toxins produced by spore-forming bacteria among people who inject drugs. The largest cluster of botulism among drug users seen so far in Europe occurred over the first 6 months of 2015, with a total of 40 cases notified to Health Protection Scotland.³ Only two cases of botulism occurred in the UK in 2017; one confirmed and one probable, both in Scotland.

The cause for this rise in incidence of wound botulism remains unclear. Injectable drugs, usually heroin, can become contaminated with bacterial spores at any point from the supply chain, from production to use. Other sources of potential contamination include the addition of drug adulterants or cutting agents widely used to increase the bulk of illicit drugs or spores present on dirty injecting equipment and the soiled hands of users.⁴ Practices such as repeated injection into the skin or muscle or the use of large amounts of citric acid also result in soft tissue damage, leading to local tissue necrosis and a favourable anaerobic environment for botulinum spores to germinate.⁵

In a case series examining a subset of 25 patients during the Scottish outbreak in 2015, the most common presenting symptom was dysarthria, with evidence of an evolving neurological deficit over the period of hours leading to ptosis, blurred or double vision, difficulty swallowing and eventually respiratory distress.³ Our patient presented with a history of dysphagia and reduced oral intake, and this formed the basis of his referral to ENT as a suspected uvulitis. Botulism was only suspected following the development of evolving bulbar paralysis on the afternoon ward round. This highlights that the presenting features of wound botulism may be vague and unfamiliar, and a high degree of suspicion among at risk patients should be ensured.

Early administration of botulism antitoxin has been demonstrated to reduce the requirement and duration of ventilatory support and time in critical care settings.^{3 6 7} The antitoxin is most effective if given within 24 hours of the onset of symptoms because the antitoxin only acts on free neurotoxin that has not yet been taken up into the motor neuron and does not reverse the action of toxin that has already disabled acetylcholine release at a neuromuscular junction.⁶ Importantly, the decision to treat should be made on clinical suspicion of botulism not laboratory confirmation, because obtaining results may take several days. Interestingly, our patient was only ventilated for 8 days in total, despite antitoxin only being administered 3 days following presentation.

The botulinum toxin may continue to be produced within the anaerobic environment of the heroin injection site, therefore surgical wound debridement should be performed to prevent disease progression irrespective of presence or absence of signs of localised infection.⁶ Antibiotic administration is important in preventing further toxin production. Clindamycin and gentamicin are avoided to limit ongoing neuromuscular blockade. Most other care is supportive.^{8 9}

Wound botulism in PWIDs has become increasingly more common in the last two decades. Lack of familiarity with the symptoms of botulinum toxicity may result in misdiagnosis and under-reporting. Early recognition is essential for the instigation of treatment to prevent progression to respiratory failure.

Learning points.

• The index of suspicion for wound botulism should be high among patients with a reported history of injection drug use.

• In contrast to other bacterial complications of injection drug use, botulism typically occurs without localised or systemic signs of infection.

• Early diagnosis should prompt antitoxin administration and respiratory supportive measures to improve survival chances.

• Surgical wound debridement and antibiotic therapy are important in preventing disease progression.