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Gorgas Case 2020-02

Diagnosis: Localized tetanus

Discussion: Based on the patient’s history and physical exam findings, a clinical diagnosis of tetanus was made. Tetanus, also known as “lockjaw”, is usually confined to developing countries and is the cause of about 10,000 deaths worldwide every year, despite being vaccine-preventable. Up to 60% of cases are neonatal and related to contamination of the umbilical stump, but the disease may also be seen in children and adults, associated with lacerations of hands and feet.

Clostridium tetani, the causative agent of this disease, is a strictly anaerobic ubiquitous Gram-positive bacillus. Some strains of C. tetani produce an exotoxin, tetanospasmin, which enters the nervous system through the myoneural junction from adjacent muscles, and can also disseminate through blood or lymph (https://www.cdc.gov/vaccines/pubs/pinkbook/downloads/tetanus.pdf). In order for the C. tetani spores to germinate and multiplicate, they must be inoculated into damaged tissue, usually with soil or other bacteria. However, it has been described that some 7% of tetanus cases may present without a point of entry (https://www.ncbi.nlm.nih.gov/pubmed/9752941).

Clinical manifestations are a consequence of the effects of tetanospasmin. There is increased muscle tone due to blockage of the inhibitor impulses of motor neurons which causes unopposed and painful intense muscle contractions. The incubation period usually ranges from 3 to 21 days, followed by progression to muscle spasms, usually within 24 to 72 hours. The first symptom is usually contraction of masseter muscles and trismus, due to the shorter length of the muscles’ axons. Three different forms of tetanus have been described. Local tetanus presents as a localized contraction of muscles in the surrounding area of the initial injury and is very rarely described. Cephalic tetanus is also rare, presenting with cranial nerve involvement after C. tetani otitis media or injuries to the head. Generalized tetanus is the most common form, presenting with a descending pattern that starts with trismus, then neck stiffness, difficulty swallowing, and rigidity of abdominal muscles. Sustained contraction of muscles in the face can cause a characteristic facies known as risus sardonicus, as seen in our case (Image A). Patients with severe spasticity may present opisthotonus (Case 10-2011, Image B), an extreme arched pose of the head, neck and spinal column caused by spasm of muscles around the spinal column. Our patient presented with a localized form: he only presented rigidity in the muscles close to the site of inoculation. No backward arching of the spine or contractions in the abdomen or upper and lower extremities occurred to indicate generalized tetanus.

The diagnosis of tetanus is clinical, as there are no characteristic laboratory or imaging findings. Only in about 30% of cases can C. tetani be isolated from the wound, although the bacteria can also be found in patients who do not have tetanus, and, as mentioned previously, not all patients will have an obvious point of entry. Other conditions that may also present with trismus include diphtheria, parotiditis, and retropharyngeal or tonsillar abscesses. Oral infections such as these will often present with fever and local pain, which helps differentiate them from tetanus. However, tetanus might also present with fever, if there is an infected portal of entry. Mandibular fractures and temporomandibular arthritis may also present with limited movement of the mouth, but careful history-taking should help discriminate between these conditions. The differential diagnosis for generalized tetanus includes varied conditions such as bacterial meningitis, hypocalcemia, rabies, strychnine poisoning, retroperitoneal hemorrhage, and spondylitis. History and meticulous physical examination are usually enough to rule these conditions out.

The severity of the disease closely correlates with time to onset of symptoms. The Tetanus Dakar score assigns one point for each of the following: time from wound to appearance to first symptom less than seven days, time from first symptom to first generalized spasm less than 48 hours, high-risk point of entry (IM injection, burns, surgery, gynecological, compound fracture, omphalitis), generalized tetanus, core temperature higher than 40°C, heart rate higher than 120/minute. A score of 0-1 is classified as mild, with a mortality of less than 10%, whereas a score of 5-6 is very severe, with a mortality rate higher than 50%. This enables the clinician to weigh the necessity of interventions such as ICU admission or tracheostomy, which is particularly useful in resource-limited settings. Other scores, such as the Tetanus Severity Score, have a better sensitivity and specificity for tetanus-associated mortality, but may be more complex to apply (https://www.ncbi.nlm.nih.gov/pubmed/16553907). Our patient had a mild form of tetanus, as judged by both scores, and his risk of mortality was low.

The initial step in management is to secure the airway. Tracheostomy is warranted in cases of severe tetanus or moderate tetanus with high risk of progression, pharyngeal or laryngeal spasm, hypoxemia or cyanosis, or if the patient requires heavy sedation. Patients should receive benzodiazepines at high doses to control muscle spasms. The current recommended therapy is diazepam at doses of 15-100mg/h, depending on disease severity, and can be combined with chlorpromazine. The IV presentation of diazepam contains propylene glycol, which can cause metabolic acidosis, so patients should be switched to oral diazepam as soon as possible. Due to this drug’s propensity to cause withdrawal reactions, midazolam and lorazepam are being studied as alternatives for long term sedation, but there is scant substantial evidence to support their use (https://pdfs.semanticscholar.org/56f3/7b127b1ad0b5cc3b95e389eeedddb19bd848.pdf). Some studies have suggested that magnesium sulphate could be used both to reduce spasms and to improve autonomic dysfunction, but evidence is still insufficient, especially for severe cases (https://www.ncbi.nlm.nih.gov/pubmed/23033859). An alternative is to combine magnesium sulphate and diazepam. Human tetanus immunoglobulin should be promptly administered to neutralize unbound toxins and prevent further symptom progression. Immunoglobulin is traditionally administered intramuscularly in the shoulder, in a single IM dose. Some guidelines recommend a dose of 3000-6000 IU; however, experts recommend using 500 IU, which appears to be equally effective. There is no apparent benefit in administering immunoglobulin around the point of entry. When human immunoglobulin is not available, equine antitoxin may be used (https://www.ncbi.nlm.nih.gov/pubmed/23949453). Several studies have shown that intrathecal administration of either human immunoglobulin or equine antitoxin may reduce muscular spasms and shorten hospital stays, with varied effects on mortality and need for mechanical ventilation. The administered product should not contain thimerosal, as this may cause arachnoiditis (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057067/). Patients should receive active immunization upon diagnosis, as tetanus does not confer lifelong immunity. Finally, necrotic tissue and foreign bodies must be removed from the point of entry to prevent further production of toxins, and patients must be started on adequate antibiotics (metronidazole is preferred; penicillin is not recommended because it is an antagonist of gamma amino butyric acid, the inhibitory neurotransmitter) (https://www.ncbi.nlm.nih.gov/pubmed/21357910). There are no specific recommendations for treatment of localized tetanus. Recovery usually takes about 4 weeks, when new synapsis form.

Due to our patient’s vaccination history and the fact that he had a contaminated wound, he should have received both the vaccine and immunoglobulin for prevention of tetanus right after his injury, as per CDC recommendations. Patients with clean wounds but unknown vaccination history or less than 3 doses of Tdap or Td should also be vaccinated (https://www.cdc.gov/vaccines/pubs/pinkbook/downloads/tetanus.pdf).

Our patient was admitted to the Intensive Care Unit, where he received treatment with 3000 IU of intramuscular human anti-tetanus immunoglobulin. He was also treated with metronidazole, diazepam, baclofen and the tetanus toxoid vaccine. He did not require high doses of benzodiazepines, and after a marked improvement in muscular rigidity, he was transferred to the internal medicine ward and discharged shortly after. On his follow-up appointment after discharge, he still felt some stiffness around the mouth but had no trouble swallowing.