A 4-year-old healthy, unimmunized girl presents to the emergency department with acute stiffness that developed in the setting of 3 days of oral refusal and decreased speech. She had 2 days of fever up to 38.7 °C and has been pointing to her head and throat when asked about pain. The girl has not had cough, congestion, or sick contacts.Her past medical history and family history are unremarkable. She is reported to have a minor lip injury sustained by accidentally running into a truck door shortly prior to the onset of her current illness. Her mother attributes her lack of immunizations to her recent immigration and not previously having established care with a pediatrician.The patient is afebrile, with a heart rate of 150 beats/min, blood pressure of 135/94 mm Hg (above the 99th percentile for age, gender, and height), respiratory rate of 15 breaths per minute, and her height and weight in the 69th and 55th percentiles, respectively. She is alert but appears distressed, making it challenging to assess localized pain. She is not responding to questions or following commands and requires assistance with a wheelchair. She has limited neck range of motion with right head deviation and bilateral jaw rigidity. The exam could not rule out meningismus. Her pupils are round and reactive to light, and eye movements are intact with no nystagmus. Her oral exam is limited due to the patient’s inability to open her mouth. However, on the buccal mucosa of her lower lip, there is a 6-mm, purple, nontender, nonindurated lesion. On neurologic examination there is generalized stiffening of the trunk and upper and lower extremities. Reflexes could not be elicited due to hypertonicity. No tremors or clonus are noted. The remainder of her examination was normal.In children, pain and anxiety can often limit their cooperation with the oral exam. However, our patient’s inability to open her mouth in the setting of neck and extremity stiffness suggests a mechanical inability, such as trismus or masseter muscle spasm.1 These symptoms suggest that generalized tetany is the primary cause of her presenting symptoms.Tetany varies in its presentation, ranging from mild, which results in localized muscle cramps, to severe, causing laryngospasm and generalized muscle spasms.2 Given the patient’s unimmunized status, tetanus was a consideration.Due to her difficult exam and generalized distress, her neck stiffness and headache made meningismus a concern. Both meningitis and encephalitis with seizures can cause loss of consciousness with intermittent muscle spasms and stiffening.3 Our patient remained alert, and her spasms and stiffening were more persistent than that seen with seizures. Cerebrospinal fluid studies did not reveal evidence of meningitis or encephalitis.One of the most common causes of tetany and trismus is electrolyte disturbance, specifically hypocalcemia.2 Hypocalcemia can be caused by hypoparathyroidism, chronic vitamin D or calcium deficiencies from dietary deficits, malabsorption, or chronic kidney disease.4,5 Nutritional hypocalcemia and vitamin D deficiency were less likely given that our patient consumed a varied diet, had no chronic history of food restriction, and did not exhibit malabsorptive symptoms. Additionally, hypomagnesemia affects the metabolism of calcium and potassium, causing hypocalcemia and hypokalemia.6 Threshold values for tetany as a consequence of hypocalcemia and hypomagnesemia are below 7.5 mEq/L and 1.2 mEq/L, respectively.7,8 Tetany due to hypokalemia can occur when the potassium level is below 2.5 mEq/L, but most cases of tetany have additional electrolyte abnormalities in addition to hypokalemia.9,10 On diagnostic evaluation, her serum calcium, phosphorus, and magnesium concentrations were normal, whereas her potassium was mildly low (3.0 mEq/L; normal 3.3–4.6 mEq/L).Neuroleptic malignant syndrome, serotonin syndrome, and strychnine poisoning were considered. However, there was no exposure history or physical exam findings associated with serotonin syndrome, such as agitation, akathisia, dilated pupils, hyperreflexia, or clonus.11 Her urine and serum toxicology results, which included assays for antipsychotics, were negative.Given the patient’s unimmunized status and concern for pharyngitis causing acute oral refusal, diphtheria was considered. Although neurotoxicity affects approximately 5% of patients, it typically presents with peripheral neuropathy and muscle weakness rather than tetany.12 Diphtheria naso- and oropharyngeal cultures were obtained and were negative.The patient’s unimmunized status, along with symptoms including the clinical triad of generalized tetanus—rigidity, muscle spasms, and sympathetic hyperactivity manifested by tachycardia and hypertension—combined with the exclusion of alternative diagnoses, confirmed the diagnosis of tetanus.13 The lip wound was biopsied and debrided by otolaryngology and found to be consistent with a possible hematoma. Biopsy revealed an interstitial neutrophilic infiltrate with no detectable microorganisms, and culture yielded scant aerobic, gram-positive rods. Wound cultures are seldom positive for Clostridium tetani, and 15% to 25% of patients present without identifiable wounds.12 Her lip wound, sustained on the truck door, was the likely source of tetanus spore inoculation.Tetanus severity can be classified by Ablett classification based on clinical features.14 Our patient’s presentation was classified as severe, with trismus, generalized spasticity, severe dysphagia, and heart rate over 120 bpm.15C tetani, an obligate anaerobic gram-positive bacillus, causes tetanus.12C tetani spores are commonly found in soil, feces, and on some metal surfaces.12 The spores typically enter the body through contaminated wounds. The bacterium produces tetanospasmin, an exotoxin that enters the central nervous system and blocks the release of inhibitory neurotransmitters, specifically gamma-aminobutyric acid and glycine, causing unopposed muscle contractions.16,17 The incubation period ranges from 1 day to 3 weeks, with a shorter duration typically associated with more severe disease.18 A combination of history, physical examination findings, and clinical suspicion leads to a diagnosis of tetanus. Tetanus typically presents with muscle stiffness and spasms in the jaw and neck, commonly referred to as “lockjaw,” which can result in dysphagia and impaired speech.19 Spasms of the pharynx or larynx may lead to acute life-threatening airway obstruction.20 Due to the relatively short axonal pathways of the jaw and facial muscles, symptoms typically manifest in these areas first before spreading to the limbs and trunk.21 Rigidity in the trunk can lead to compromised chest wall compliance and respiratory failure. Disinhibited discharges disrupt autonomic control, causing elevated plasma catecholamines, which results in sympathetic hyperactivity.22 Recovery from tetanus toxin is reliant on the regeneration of new nerve terminals and the degradation of the toxin that binds irreversibly to receptors.17Tetanus incidence has declined following the development of the tetanus toxoid–containing vaccine, which has a clinical efficacy of nearly 100% with a complete series.23 According to the National Notifiable Disease Surveillance System, from 2013 to 2022, there were 267 reported tetanus cases resulting in 13 fatalities. Of those cases, 200 either lacked or had incomplete vaccination records.24 Vaccination rates have generally declined since the COVID-19 pandemic. Ten years prior to the pandemic, vaccination rates for children entering kindergarten were 95% for all vaccines. By the 2022 to 2023 school year, the rate dropped to 93%.25 Additionally, people who are US refugees and immigrants have overall lower vaccination rates compared to US-born individuals, increasing their risk of vaccine-preventable diseases.24 According to US immigration law, individuals applying for visas or permanent residence are required to submit a Report of Medical Examination and a vaccination record with their application or risk being denied.26 People who are refugees are not required to complete the vaccination requirements during their initial medical examination outside of the United States.27 Barriers to continued vaccination for both populations include poor access to care, cultural bias, knowledge gaps, and distrust of the medical system.28Tetanus is considered a medical emergency with a case-fatality rate approaching 100% without treatment and 10% to 20% with treatment.23 Given the high risk of airway compromise and lethality rate for under treatment, patients with suspected tetanus require admission to the intensive care unit.29Regardless of severity and vaccination status, treatment focuses on neutralizing unbound toxin with tetanus immune globulin, preventing further toxin proliferation with antibiotics, wound debridement if necessary, and symptomatic management while awaiting neuronal regeneration.29 Both metronidazole and penicillin are effective treatments for tetanus. However, metronidazole is the preferred agent, as there is a risk of precipitating seizures with penicillin.16,29 The recommended duration for metronidazole is 7 to 10 days.16,30 Debridement of contaminated wounds reduces the ongoing release of toxins.14 Effective management of muscle rigidity and spasms is essential for patient comfort. Medications that are used to address tetany include benzodiazepines, baclofen, propofol, and nondepolarizing neuromuscular blocking agents.15 Additionally, minimizing stimulation, such as keeping the patient in a quiet, dimly lit room and clustering care, can help reduce sensory input, preventing worsening spasms.14,29 Patients often require supplemental enteral nutrition due to a combination of increased metabolic needs, increased sympathetic activity, and poor oral intake from trismus.15 The vaccine series for diphtheria, tetanus, and acellular pertussis should be initiated as soon as the patient is stabilized and before discharge, as acute infection does not confer immunity.31 For patients 4 years of age or older, a 4-week interval is recommended between doses 1, 2, and 3, and a 6-month interval between doses 3 and 4.31 A delay in the diagnosis of tetanus can result in severe morbidity and a need for prolonged inpatient rehabilitation for complete recovery. These complications not only impact patient outcomes but also impose a significant financial burden on the health care system.Our patient was hospitalized in the pediatric intensive care unit and treated with tetanus immune globulin, metronidazole, diazepam, and nasogastric feeding. Diazepam effectively alleviated her muscle rigidity, spasms, and lockjaw. Efforts to minimize stimulation, including reducing vital sign assessments and clustering care, were implemented to mitigate spasms. She was hospitalized for 12 days, 4 of those in the pediatric intensive care unit. Upon hospital discharge, the patient returned to her baseline motor function, oral feeding, and verbal communication. The patient’s mother agreed to initiate vaccinations based on the Centers for Disease Control and Prevention catch-up schedule before discharge.Tetanus should be suspected in an unimmunized patient presenting with muscle spasms, rigidity, and signs of sympathetic hyperactivity.Tetanus is typically diagnosed clinically, with positive findings from cultures or laboratory investigations being rare.The differential diagnosis of childhood tetany includes infections, electrolyte abnormalities, and ingestions.Thank you to Dr Sanyukta Desai, MD and Dr John Luk, MD for review of this manuscript.
Pham et al. (Wed,) studied this question.