Hrev_master [page 74] [Emergency Care Journal 2018; 14:7410] Emergency Care Journal 2018; volume 14:7410 Abstract Tetanus with cephalic involvement is not a typical presentation of the disease; characteristic signs and symptoms are strictly local- ized in cranial district, although it could frequently progress to the classical generalized form. Tetanus is still spread worldwide, espe- cially in particular subgroups as elderly and newborn babies and in countries with an inadequate vaccine coverage. We report a case of an adult man with generalized tetanus with cephalic presentation in Emergency Department. We aim to outline how difficult it was to diagnose in an adult patient without apparent exposition of previ- ous minimal trauma or injury because of a lot of confusing factors and slow progressing clinical signs. Prompt recognition of signs and symptoms, opportune target therapy and supportive care, in association with correct vaccination schedule, are paramount to determine the prognosis for affected patients. Case Report A 58-year-old man presented himself to our Emergency Department reporting progressive speech impairment caused by bilateral pterygoid and masseter muscles contraction since about one week, accompanied by dysphagia with some episodes of fluids and saliva inhalation. He had no history of smoking or chronic disease or medica- tions. He worked as a Forest Ranger and practiced jogging regular- ly. He was affected by chronic sinusitis so he performed a surgical intervention of Functional Endoscopy Sinus Surgery about one month before (33 days before). His last tetanus boosting dose was 13 years before but he had no recent history of wounds or animal bites. On physical examination vital signs were normal, the patient was afebrile and revealed a strong and painful contracture of mas- seterine, pterygoids and platysma muscles bilaterally allowing a maximum mouth opening of about 1 cm. He had sialorrhea but his cough reflex was preserved. Any attempt to drink water elicit- ed spasms and a choking sensation. There wasn’t any evidence of local infection or cutaneous wounds and blood exams were in the normal range (Table 1). The neurologic examination did not reveal any focal features, sensory changes or abnormalities in coordination. Differential diagnosis The differential diagnosis in a case of isolated lockjaw and difficulty swallowing is a challenging trial to face for the Emergency Physician. Since symptoms were strictly localized in the cranial district, with a history of a recent procedure in the same area involving implantation of a surgical prosthesis, we initially suspected a sur- gical complication (infective or nervous and muscular impair- ment). As a consequence we asked for a Ear Nose and Throat con- sult in the Emergency Department. At the specialist’s evaluation there were no signs of infection of oral mucosa or teeth, no lesions or pain on the site of intervention, no bleeding or wounds in the oral cavity, no abscess in the cervical or facial area; so probabili- ties of a surgical complication seemed to diminish. Moreover, the absence of malocclusion or joint clicking on examination ruled out the hypothesis of a temporomandibular joint dysfunction causing the symptoms.1 Hypocalcemic tetany could be quickly ruled out by detection of normal serum levels of total and ionized calcium.1 Among other conditions associated with muscle spasms, there are also Malignant Neuroleptic Syndrome, Serotonin Syndrome, Dystonic reactions and Stiff-Man Syndrome, but none of these seemed likely because the patient’s history was negative for taking of medications and the overall clinical presentation didn’t suggest any of these diseases.1,2 Some features of this case could remind of Rabies presenta- tion, such as excess salivation and spasms triggered by attempts to drink water, which could be interpreted as hydrophobia. However, a history of animal bite was lacking and the integrity of neurolog- ical status was not consistent with rabies encephalitis.3-5 The remaining most likely hypothesis was tetanus, in which sensorium is unimpaired while trismus and spasms of deglutition muscles may result in difficulty with swallowing and verbal expression. However, a history of infection was lacking and the subacute onset of the symptoms wasn’t typical for the disease. In this case, the localization of symptoms in the cranial district could depend either on a subacute form of cephalic presentation or, even more uncommon, on a localized form of post-surgical Correspondence: Giulia Marullo, Emergency Department, Bicocca University of Milan, ASST Grande Ospedale Metropolitano Niguarda, Piazza Ospedale Maggiore 3, 20161, Milano. Tel.: +39.02.64447433. E-mail: giulia.marullo@gmail.com Key words: Lockjaw; Tetanus; Emergency department. Contributions: the authors contributed equally. Conflict of interest: the authors declare no potential conflict of interest. Funding: none. Received for publication: 10 March 2018. Revision received: 25 June 2018. Accepted for publication: 29 June 2018. This work is licensed under a Creative Commons Attribution 4.0 License (by-nc 4.0). ©Copyright G. Marullo et al., 2018 Licensee PAGEPress, Italy Emergency Care Journal 2018; 14:7410 doi:10.4081/ecj.2018.7410 A case of lockjaw in the emergency department Giulia Marullo,1 Giulia Maria Bottani,1 Rossella Guerrieri,2 Adriano Basile,2 Paolo Aseni,2 Andrea Bellone2 1Emergency Department, Bicocca University of Milan; 2Emergency Department, Niguarda Hospital, Milan, Italy Non -co mmerc ial us e o nly [Emergency Care Journal 2018; 14:7410] [page 75] tetanus. The latter is linked to an exogenous contamination of spores in the site of surgery (favoured by necrotizing tissues or presence of foreign bodies such as prosthesis) or to an endogenous transmission by the use of contaminated equipment. Moreover, post surgical tetanus develops quickly, usually within 24 hours.3,6 Perfectly mimicking tetanus, strychnine poisoning could be another possible causative agent of muscle spasms and trismus in the absence of alteration of mental status but this condition is char- acterized by an acute onset, a generalized spread of the spasms and a rapid, often fatal course of the disease if not treated.1 Clinical course During some hours of observation in the Emergency Department the patient remained symptomatic for painful contrac- tions of facial muscles and strong lockjaw. Even if an early expert opinion from an Infectious Diseases clinician couldn’t rule out or confirm our main suspicion of tetanus, we finally agreed upon a broad spectrum strategy, to pro- tect the patient from common infective agents and tetanus risk. A dose of 500 UI Human Tetanus Immunoglobulin (HTIG) was given intramuscularly along with a single dose of tetanus vaccine with tetanus toxoid. We started an antibiotic coverage with metronidazole 500 mg tid and ampicillin 3 g qid. An early inten- Case Report Table 2. Differential diagnosis of tetanus. Table 1. Test results in the emergency department. Non -co mmerc ial us e o nly [page 76] [Emergency Care Journal 2018; 14:7410] sivist evaluation suggested starting with intravenous benzodi- azepines and baclofen. The patient was admitted to Emergency Medicine Unit for a strict hemodynamic and respiratory observation. The results of plasmatic tetanus immunoglobulin levels revealed to be insuffi- cient for an appropriate tetanus coverage (IgG: 0,01 UI/mL). Electromyography (EMG) was performed and showed a bilateral absence of physiologic answers (Sp1 and Sp2) of masseterine inhibitory reflex. This exam consists of an electric stimulation during massive masseterine contraction; Sp1 is a silent inhibito- ry period that lasts about 10-15 seconds, Sp2 is the following inhibitory one of 40-50 seconds. This neurophysiological result suggested cephalic tetanus.7 In the meantime, on the second day from admission, we observed a rapid worsening of lockjaw and sialorrhea a progres- sion of muscular contractions with the involvement of thoracic muscles, a consequent onset of respiratory distress, hypoxic-hyper- capnic acute respiratory failure and respiratory acidosis. At this stage, the clinical course along with laboratory and neu- rophysiological findings were all consistent with a diagnosis of generalized tetanus with a cephalic onset. Hence, a second dose of 5500 UI intravenous HTIG was administered, reaching a total of 6000 UI. A maxillofacial surgeon’s evaluation excluded any possibility for surgical debridement in the absence of even minimal wound infection. Hence, our patient underwent curarization and oro-tracheal intubation and was transferred to Intensive Care Unit (ICU), where he was treated with mechanical ventilation for 17 days. Antibiotic therapy was continued. After a few days, a tracheostomy was per- formed, and the man underwent progressive respiratory weaning until reaching of complete normal breathing pattern. In that period enteral nutrition by nose-gastric tube was started; benzodi- azepines and baclofen therapy was continued with a progressive and gradual dosage reduction according to patient improvement. After seven days in ICU, the clinical course was complicated by MSSA nosocomial pneumonia, treated with levofloxacin and amoxicillin/clavulanate with a good response. The patient started physical rehabilitation of swallowing, oral and full motor move- ments with intensive muscular physiotherapy obtaining an excel- lent global recovery in two months. We then performed a second dose of vaccine with tetanus toxoid. Two months later, a second EMG was performed showing a weak silent masseterine time after mandibular nerve stimulation (Sp1 inhibitory reflex), while a Sp2 answer absence. The patient returned home after two months of stay in good general conditions; our final diagnosis was gener- al tetanus with cephalic onset (Table 2). Tetanus: clinical outline of the disease Tetanus is a toxin-mediated disease produced by the bacterium Clostridium tetani characterized by generalized rigidity and mus- cle spasms that may cause respiratory arrest and death. It is char- acterized by various forms and presentations, even though it would be entirely preventable by a specific vaccine.3,8 Nowadays it is still spread worldwide, especially in South East Asian and African countries, reaching a maximum in regions as Nigeria and India, where population’s vaccine coverage is still inadequate. However, cases are diminishing in these regions as well. Incidence in Europe and USA is 0.01/100.000 inhabitants,9,10 mostly in the elderly. With increasing age, the human immune system undergoes immunose- nescence, which leads to insufficient protection following vaccina- tion; response to tetanus vaccination in the elderly was evaluated in a study on people over 60 years old demonstrating that single shot vaccinations did not lead to long-lasting immunity.11-13 The higher incidence of tetanus in the elderly seems to be mainly due to the lack of tetanus toxoid boosting doses. There is little literature about this topic; an Italian study showed a progressive rise in uncovered population in elderly, reaching about 80% in people ove 80 years old. Incidence was higher in females; the most probable explanation for this phenomenon is that males are usually vacci- nated during the military service and/or receive booster vaccina- tion after injury more frequently. Similar results are showed in a European study; available data, for a few number of countries, demonstrates an insufficient seroprotection in oldest groups. The causative agent of tetanus is Clostridium tetani, a Gram- positive anaerobic bacillus. It is a common host of the gastroin- testinal tract of many animals (like sheep, horse, cow, cat) and in the soil in the form of spores. It represents a continuous threat especially for more vulnerable subgroups, like elderly or new- borns. Around the world, there are many cases of neonatal tetanus for delivery from non-immune mothers, umbilical cord’s cut and perinatal care in non-sterile conditions.3,14 Transmission is from continuous cutaneous solution, there is not an inter-human transmission. Infection is strictly localized in entrance site as a wound, burned tissue or umbilical cord. Source is not always identifiable, with rates of cryptogenic tetanus as high as 23%.3 Anaerobic conditions allow spore germination with pro- duction of tetanic toxins as tetanospasmin. Toxin’s targets are central inhibitory interneurons, glycinergic and GABAergic: the interruption of release of these neurotransmitters determines an uncontrolled activity of motoneurons (alpha and gamma) and auto- nomic nerves. It follows muscular spasms, hypertonic muscle activity and disregulation of the autonomic system.3,14 Clinical presentation can be generalized, neonatal and local- ized cephalic form with an incubation period in adults is 3-21 days, median 8 days. A progression of respiratory failure and hemody- namic instability is frequently observed.1,3,8 Diagnosis relies on clinical diagnosis. Determination of plas- Case Report Table 3. Treatment. Non -co mmerc ial us e o nly [Emergency Care Journal 2018; 14:7410] [page 77] ma Immunoglobulin levels (IgG) is useful for defining vaccine status and possible susceptibility to disease; generally, a plasmatic concentration above 0,1 UI/mL is considered to be protective.3 Microbiological culture is insensitive and unspecific with positiv- ity in about 30% of cases.3,8 The EMG can be helpful to support clinical diagnosis.7 Standard therapy requires Intravenous 6000UI HTIG, or a first intramuscular 500 UI HTIG dose near the site of infection and an intravenous 5500 UI one. However, according to some authors, a dose of 500 units IM appears as effective as larger doses;15,16 literature is still debated. Antibiotic coverage is usually recommended. Supportive care with antispastic agents (benzodi- azepines and baclofen), magnesium sulfate, adequate airway man- agement by orotracheal intubation and mechanical ventilation, neuro-muscular blocking drugs, and hemodynamic support are often required. Early wound debridement is recommended after prophylactic HTIG administration, in order not to diffuse a big- ger amount of circulating toxin. Appropriate tetanus prophylaxis should be administered as soon as possible following tetanus- prone wounds injury with HTIG 250 UI IM. However, a dose of HTIG 500 UI should be given also to late presenting patients and to penetrating trauma victims because incubation period is quite variable. For patients who have been previously vaccinated against tetanus but are not up to date there is little benefit in administering human tetanus immune globulin more than one week after the injury. However, for patients thought to be completely unvaccinat- ed, human tetanus immune globulin should be given up to 21 days following the injury and tetanus toxoid should be given to such patients. All affected patients should receive a complete immunization cycle, regardless of previous immunization history. The amount of pathogenetic toxin during the disease is not suffi- cient to elicit a long lasting immune response.3,8 A detailed table (dose, route of administration, length of thera- py) with therapy (immunization, benzodiazepines/ Propofol/baclofen, Magnesium infusion, Vecuronium/cisatracuri- um/pancuronium) it would be helpful (Table 3). Prognosis: We couldn’t find reliable data about mortality rates. This could be due to tetanus’s rapid onset and highly lethal conse- quences, justifying the absence of randomized controlled trials eth- ically unacceptable and observational studies in a patients with or without symptomatic and specific therapy. Conclusions Treating patients with tetanus is a rare event in industrialized countries and awareness is needed to recognize early signs of this serious disease. Our patient’s case was unusual because he had a history of previous immunization and at presentation he had vague symptoms and no defined portal of entry. However, his levels of tetanus antibodies were undetectable. This finding reflects the par- ticular risk for tetanus in adult patients who could have been vac- cinated many years before and outlines the importance of renewing adequate tetanus immunization to the whole population. We hypothesize that the subacute course of the disease in our patient could be partly justified by the previous immunization. Tetanus can present with unusual clinical forms and therefore, this diagno- sis should be taken into consideration in the Emergency Department even in poorly symptomatic patients and in acute dys- phagia. 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