A 38-year-old Hispanic male who immigrated from Ecuador in 2001 and who, at the time of his initial presentation, had been working in construction, landscaping and masonry, presented to our emergency department (ED) with a chief complaint of trismus, voice changes, stiffness, and tremors. At the time of his presentation to our ED, he had already had two prior ED visits elsewhere, where he was treated with nonsteroidal anti-inflammatories, prednisone, and cyclobenzaprine that did not offer any significant relief.

The patient’s third ED visit occurred about 10 days after the initial onset of symptoms with reports of worsening of all the aforementioned symptoms, impairing his ability to ambulate and eat. He denied a history of any recent cuts or open wounds, tick bites, headache, fever, or rash.

Physical exam revealed a non-intoxicated middle-aged gentleman sitting in a wheelchair, requiring assistance from his wife to ambulate. His vital signs were normal and his exam was notable for trismus, mild voice muffling, left lower extremity rigidity, 3+ brisk reflexes throughout, and right ankle clonus. Diphenhydramine was initially attempted for treatment of presumed dystonic reaction. This treatment was unsuccessful.

Hospital Course

Given the history provided along with exam findings, tetanus was high on the differential diagnosis. He was given a tetanus toxoid injection, started on metronidazole, and was given tetanus immune globulin. Neurology and infectious-disease teams were contacted and the patient was admitted to the hospital under the neurological service. Initial laboratory exams were unremarkable, including a normal serum lactate, complete blood count, comprehensive metabolic panel, troponin, respiratory multiplex, and thyroid stimulating hormone.

The infectious disease consult team agreed with the diagnosis of potential tetanus infection with a possible source being spore inhalation considering his type of work; strychnine poisoning was also raised as a consideration. During his admission, he was continued on treatment for suspected tetanus infection and had further inpatient testing with the following results: tetanus antitoxoid antibodies: <10 (recall he was last vaccinated for tetanus 12 years prior) and a serum drug screen which was positive for diazepam, nordiazepam, and metronidazole. His strychnine level was negative. The rest of the workup, including MRI of the brain and cervical spine with and without contrast, were unremarkable.

The patient received metronidazole and diazepam during admission with some improvement of his symptoms and was discharged to rehabilitation with instructions to continue metronidazole for 10 days and follow up with the infectious-disease clinic to complete his tetanus toxoid vaccine series. During his follow-up visit, the patient was found to have improvement of symptoms along with a left popliteal fossa wound that was considered the true source of his tetanus.

Discussion

The patient reported his last Tdap was 12 years prior. Tetanus occurs when spores of Clostridium tetani, an obligate anaerobe normally present in the gut of mammals and widely found in soil, gain access to damaged human tissue. After inoculation, C. tetani produces the metalloprotease tetanus toxin (also known as tetanospasmin). The incubation period of tetanus is approximately eight days but ranges from three to 21 days.¹

After reaching the spinal cord and brainstem within the motor neuron, tetanus toxin is secreted and enters adjacent inhibitory interneurons, where it blocks neurotransmission by its cleaving action on the membrane proteins involved in neuroexocytosis.^2-5 The net effect is inactivation of the inhibitory neurotransmission that normally modulates anterior horn cells and muscle contraction. This loss of inhibition of anterior horn cells and autonomic neurons results in increased muscle tone, painful spasms, and widespread autonomic instability.

The most common and severe clinical form of tetanus is generalized tetanus. The presenting symptom in more than 80 percent of such patients is trismus (lockjaw) but they may present with tonic and periodic spastic muscular contraction such as stiff neck, opisthotonos, risus sardonicus (sardonic smile), a board-like rigid abdomen, periods of apnea and/or upper airway obstruction due to vise-like contraction of the thoracic muscles and/or glottal or pharyngeal muscle contraction, and dysphagia.

Patients with generalized tetanus typically have symptoms of autonomic overactivity that may manifest as profuse sweating, tachycardia, cardiac arrhythmias, labile blood pressure, and fever.

Modern Management of an Ancient Disease

Tetanus-toxin-induced effects are long-lasting (up to four to six weeks) because recovery is believed to require the growth of new axonal nerve terminals.

The recommended treatment for tetanus is:

1. Human tetanus immune globulin is the antitoxin of choice to neutralize unbound toxin. The Centers for Disease Control and Prevention recommends a single dose of 500 units intramuscularly (IM).^1,6
2. Since tetanus does not confer immunity following recovery from acute illness, all patients with tetanus should receive active immunization with a full series of tetanus- and diphtheria-toxoid-containing vaccines, immediately upon diagnosis. Such vaccines should be administered at a different site than tetanus immune globulin.
3. Metronidazole (500 mg intravenously [IV] every six to eight hours) is the preferred treatment for tetanus, but penicillin G (2 to 4 million units IV every four to six hours) is a safe and effective alternative.⁸ Treatment duration of seven to 10 days is recommended.
4. In patients with severe tetanus, the mainstay treatment is additional supportive care as needed. This may include mechanical ventilation and benzodiazepines as needed for spasticity.

Accidental or intentional strychnine poisoning may produce a clinical syndrome similar to tetanus and should be strongly considered in a patient who is fully vaccinated or has no obvious wounds. Strychnine was first used as a rodenticide in Germany in the early 16th century. Although rare, most strychnine poisonings today result from the adulteration of street drugs (e.g., cocaine, heroin) as well as from small amounts found in herbal medications and homeopathic remedies.⁷

The case presented above, with a classic picture of tetanus, is an infrequently seen disease process in the United States but offers excellent learning opportunities.

Key Points

• Spore inhalation may be a source of tetanus even if there are no open wounds.
• Trismus that presents without an associated oropharyngeal source should raise concern for tetanus.
• Treatment includes cleaning the wound, halting the toxin, neutralization of the unbound toxin, antibiotics, and supportive management.
• Strychnine poisoning may produce a clinical syndrome similar to tetanus and should be strongly considered in a patient who is fully vaccinated or has no obvious wounds.

Dr. Johnson is a board-certified emergency physician. He serves as the point of care emergency ultrasound director for two hospital sites within his network and enjoys teaching. Dr. Johnson has given many ultrasound lectures to different services within the hospital including the emergency department and surgical team. He continues to lead two emergency departments in POCUS and ultrasound training.

Yehudis Weiss has been practicing as a physician assistant since 2011 and is currently working in the emergency department at Westchester Medical Center in Westchester, N.Y., where she has been for the past eight years.

References

1. Centers for Disease Control and Prevention. Epidemiology and prevention of vaccine-preventable diseases. Tetanus. CDC website. https://www.cdc.gov/vaccines/pubs/pinkbook/tetanus.html. Published August, 2021. Accessed February 15, 2023.
2. Lalli G, Bohnert S, Deinhardt K, et al. The journey of tetanus and botulinum neurotoxins in neurons. Trends Microbiol. 2003;11:431.
3. Deinhardt K, Berninghausen O, Willison HJ, et al. Tetanus toxin is internalized by a sequential clathrin-dependent mechanism initiated within lipid microdomains and independent of epsin1. J Cell Biol. 2006;174:459.
4. Schiavo G, Benfenati F, Poulain B, et al. Tetanus and botulinum-B neurotoxins block neurotransmitter release by proteolytic cleavage of synaptobrevin. Nature. 1992;359:832.
5. Caccin P, Rossetto O, Rigoni M, et al. VAMP/synaptobrevin cleavage by tetanus and botulinum neurotoxins is strongly enhanced by acidic liposomes. FEBS Lett. 2003;542:132.
6. Tetanus (lockjaw). In: Pickering LK, Baker CJ, Kimberlin DW, Long SS, eds. Red Book: 2009 Report of the Committee on Infectious Diseases, 28th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2009:655.
7. Chan TY. Herbal medicine causing likely strychnine poisoning. Hum Exp Toxicol. 2002; 21:467.
8. Afshar M, Raju M, Ansell D, Bleck TP. Narrative review: tetanus-a health threat after natural disasters in developing countries. Ann Intern Med. 2011;154:329.