|Year : 2018 | Volume
| Issue : 2 | Page : 81-86
Fatal tetanus infection originating from fungating advanced breast cancer: Case report and review of the literature
Abdullahi Adamu1, Zubair Hadi Ismail1, Muhammad Inuwa Mustapha2, Sefiya Adebanke Olarinoye-Akorede3
1 Department of Radiotherapy and Oncology, ABUTH, Zaria, Nigeria
2 Department of Radiology, Oncology Unit, AKTH, Kano, Nigeria
3 Department of Radiology, ABUTH, Zaria, Nigeria
|Date of Web Publication||30-May-2019|
Dr. Abdullahi Adamu
Department of Radiotherapy and Oncology, Ahmadu Bello University Teaching Hospital, Zaria -810001, Kaduna State
Source of Support: None, Conflict of Interest: None
Tetanus is an acute and potentially fatal disease caused by an exotoxin produced by a bacterium, Clostridium tetani. The cultural habit of application of concoctions made from mud and animal dung to chronic and necrotic wounds in our environment may provide a portal of entry for serious tetanus infection. There is a paucity of published data of tetanus infection arising from a necrotic breast tumor as a possible portal of entry in study area necessitating our report on a 48-year-old woman with extensive and fungating invasive ductal carcinoma of the breast who acquired fatal tetanus infection presumably from application of animal dung to the necrotic chest wall tumor. Patient and caregiver's education, clinical awareness, timely treatment, and proper tetanus vaccination in predisposed patients before surgical excision, debridement, or chemotherapy might be necessary to prevent this catastrophe.
Keywords: Breast cancer, management, spasms, tetanus
|How to cite this article:|
Adamu A, Ismail ZH, Mustapha MI, Olarinoye-Akorede SA. Fatal tetanus infection originating from fungating advanced breast cancer: Case report and review of the literature. Arch Int Surg 2018;8:81-6
|How to cite this URL:|
Adamu A, Ismail ZH, Mustapha MI, Olarinoye-Akorede SA. Fatal tetanus infection originating from fungating advanced breast cancer: Case report and review of the literature. Arch Int Surg [serial online] 2018 [cited 2019 Oct 18];8:81-6. Available from: http://www.archintsurg.org/text.asp?2018/8/2/81/259464
| Introduction|| |
Tetanus has remained a public health problem and a major contributor to morbidity and mortality in developing countries such as Nigeria despite the availability of effective vaccines. Clostridium tetani (C. tetani), the causative organism, is widespread in the feaces of domestic animals and humans while the spores are abundant in soil and in the environment surrounding the habitations of humans and animals. A potent neurotoxin, tetanospasmin, produced under anaerobic conditions in wounds contaminated with the bacterial spores is responsible for the clinical manifestations of tetanus, which remains one of the world's major cause of preventable deaths with an estimated incidence of about a million cases per annum with mortality rates as high as 28/100,000 in developing countries and 0.1/100,000 in North America. In 2002, tetanus caused an estimated 180,000 deaths worldwide. Among patients admitted for neurologic conditions at the University College Hospital, Ibadan, Nigeria, tetanus was the second most common cause of adult neurologic admission (14.2%) after stroke. There is no data on the incidence of tetanus in breast cancer patients in our environment. Tetanus is associated with severe neurological, cardiovascular, respiratory and renal complications with associated physical and psychological affectation., It typically presents with trismus, difficulty in swallowing, and more ominously difficulty in breathing, or opisthotonos. The goals of therapy of a tetanus patient are to eliminate the source of toxin, neutralize unbound toxin, and prevent or abort muscle spasms, monitoring the patient's condition and providing respiratory support until recovery.
We report here the case of a patient with tetanus infection. The reported patient is a 48-year old woman with invasive breast cancer whose presumed infectious foci were the application of concoctions containing mud and cow dung to the extensive breast mass wounds, thus illustrating the problem between harmful cultural practices, poverty, and ignorance among many of our cancer patients and their caregivers.
| Case History|| |
A 48-year-old para (p) 6+1(all her pregnancies and deliveries were at home and unsupervised) woman diagnosed a year ago with histologically confirmed infiltrating ductal carcinoma of the left breast (stage III). Immunohistochemistry showed estrogen and progesterone receptor positivity and HER2-negative. She presented to the accident and emergency department with dysphagia, spontaneous spasms of the extremities, and trismus. The symptoms started about 4 days before admission and had progressively became worse. The breast mass was reported to have ulcerated 4 months earlier and have progressively increased in size and extended to involve the contralateral right breast. Patient could not come to hospital because of financial constraints, but instead patronized a traditional/alternative medicine practitioner in their locality who gave concoctions made from mud, dried leaves, and cow dung. She started applying this concoction to the anterior chest wall wound for 2 weeks before presentation and is presumed to be the source of infection.
The patient refused mastectomy 9 months before and after completing three courses of neoadjuvant chemotherapy consisting of intravenous 5-fluorouracil 600 mg/m2, cyclophosphamide 600 mg/m2, and adriamycin 50 mg/m2 administered at 3 weekly intervals subject to satisfactory biochemical and hematological parameters. The chemotherapy was well tolerated with significant tumor regression achieved: from an inoperable tumor mass of 12 cm by 10 cm by 8 cm to an operable 4 cm by 3 cm by 1.5 cm. She was also commenced on tamoxifen 20 mg daily (on account of estrogen receptor and progesterone receptor positivity), which she equally stopped after 3 months. She was lost to follow up until her presentation to the emergency unit.
General examination revealed an ill-looking woman, afebrile, conscious, and alert. She was lying very still with the neck retracted in an opisthotonic posture. She had severe trismus and could not speak or swallow. Attempts to examine the oral cavity increased the trismus. She developed generalized muscle spasms lasting about 1 min per episode spontaneously and with any movement. Spasms recur about once every 30 min. Her blood pressure was 120/70 mmHg with a heart rate of 80 beats per minute. Her respiratory rate was 36 cycles per minute with occasional apneic spells. Generalized spasticity was also elicited in the musculoskeletal system. The rest of the examination was unremarkable.
Examination of the chest wall revealed an ulcerated, necrotic tumor involving the left breast and extending to the contralateral breast [Figure 1]. The base exuded foul-smelling green-colored discharge and was covered with dried leaves, mud, and cow dung. Based on the presence of trismus, rigidity of the neck, and reflex spasms, she was admitted as a case of severe tetanus based on clinical diagnosis. A tracheostomy tube was inserted for her, and she was immediately given 1000 IU of human anti-tetanus immunoglobulin (HTIG) to neutralize unbound tetanus toxin and 0.5 ml tetanus toxoid vaccine as an active immunization. Both were given via the intramuscular route on alternate gluteal muscles. She was also placed on oxygen via nasal prongs at a rate of 5 l/min, intravenous metronidazole 500 mg every 6 h, and intravenous ceftriaxone 1 g every 12 h (both were administered to reduce bacteremia of C. tetani and as broad antibiotic for wound sepsis). Intravenous diazepam, 30 mg every 4 h, was initiated to sedate the patient and control the spasms.
|Figure 1: Extensive and fungating anterior chest wall ulcer due to advanced breast cancer in a woman presenting with tetanus|
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Initial laboratory data revealed white blood cells count of 26,900/l, and electrolyte, urea, and creatinine values were within normal limits. Wound aspirate grew polymicrobial growth including Klebsiella pneumoniae and Pseudomonas aeruginosa. Debridement of the wound on the breast mass was deferred due to anticipated excessive bleeding but was dressed daily.
In the following 48 h after admission, patient's clinical condition deteriorated with more prolonged reflex spasms, increased respiratory rate of 60, more frequent apneic spells, and a tachycardia of 140. There was severe hypertension of 170/110 alternating with hypotension and brachycardia. Despite our intervention with intravenous labetalol, morphine, magnesium sulfate, and increased dose of diazepam to 60 mg every 6 h with appropriate hydration, patient eventually died after 5 days on admission due to ventricular fibrillations.
| Discussion|| |
Tetanus is a devastating disease associated with a high morbidity and mortality. On the basis of the presence of trismus, rigidity of the neck, and reflex spasms, the patient was admitted and managed as a case of tetanus in conformity with the World Health Organization recommendation of at least one of the following signs for diagnosis of tetanus: trismus, risus sardonicus, or painful muscular spasms. This is because the diagnosis of tetanus is entirely clinical with no characteristic laboratory findings. Common points of entry of the C. tetani spores include animal bites, burns, puncture wounds, intravenous drugs use, and chronic and necrotic nonhealing wounds. Moreover, in about 15–25% of patients, no recent wound can be identified. There are some reports of tetanus in patients with tumors including soft tissue sarcoma, uterine leiomyoma, and ulcerating giant phyllodes breast tumor. Our patient, to our knowledge, is the first reported case of tetanus infection from a breast wound in our environment. The presumed point of entry of C. tetani spores was probably from application of traditional concoctions containing different substances including mud and animal dung to the breast tumor. The necrotic breast tumor may provide an excellent anaerobic environment for the spores to thrive leading to clinical tetanus in this patient. The risk for the development of clinical tetanus in this patient is increased by the presence of the chronic chest wounds, immunocompromised state from the cancer and its treatment (the neoadjuvant chemotherapy she had received), and the psychological stress of cancer. All these factors might have contributed to the alteration and depression in her immune status and thus increased her risk for tetanus infection.,
The management of patients with tetanus requires simultaneous attention to several concerns; including maintenance of airways patency, passive immunization, elimination of source of toxins, neutralization of unbound toxin, prevention and/or aborting muscle spasms, and respiratory support until recovery.
HTIG was administered to neutralize circulating and unbound toxin in the wound, this effectively shortens the course of tetanus and lowers it mortality and is aimed at eliciting an effective and lasting immune response against C. tetani. However, some studies report that there is little or no long-lasting effective immunity conferred by an attack of tetanus or by injection of passive toxoid. This may explain the poor response of our patient to this intervention as the time of administration of HTIG was too short for her body to elicit normal antibody rise in response to the vaccination. This is the more likely as she had never received tetanus vaccination even during her pregnancies. Cases of chronic malignant wounds may therefore warrant periodic administration of antitoxin until the wound is healed or active immunity had been confirmed.,,
Active immunization with adsorbed tetanus toxoid as tetanus–pertussis–diphtheria or tetanus–diphtheria vaccine concurrent with HTIG is controversial, as some experts believed active immunization should be commenced when the patient is more stable or prior to discharge from the hospital, so as to prevent the possible neutralizing effect of HTIG on the tetanus toxoid and thereby making active immunization ineffective., We administered 0.5 ml of the tetanus toxoid in the form of tetanus–pertussis–diphtheria vaccine on the contralateral gluteal muscles within 24 h of her presentation to hospital. This is to serve as an active immunization.
A single dose of tetanus toxoid ensures little or no protection even among immunocompetent subjects. Immunity develops only 2–4 weeks after the second dose and even then, about 10% of patients, labeled “bad responders,” remain poorly protected. Moreover, immunity decreases over time, with the percentage of poorly protected persons increasing after just 1 year. It is the third dose that induces significant levels of antitoxin such that protection can last at least 5 years. Additional doses given at least 1 year after the last dose prolongs immunity even further, lasting 10 years after the fourth dose and 20 years after the fifth. This suggests that giving tetanus toxoids during bouts of tetanus and on follow up will only protect the individual from tetanus at the very earliest 2 weeks after the second dose is given. Hence, to prevent recurrent tetanus, the focus should be to prevent primary tetanus from occurring in the first place. Otherwise, an individual previously not vaccinated against tetanus (as is the case with our patient in spite of six deliveries) is prone to recurrence within 6 weeks of being given the first tetanus toxoid vaccine. This informed our decision to commence tetanus toxoid and be followed by booster doses at specified intervals using the World Health Organization recommendations for tetanus vaccination. The most recent recommendation of the US Centers for Disease Control and Prevention and the World Health Organization for primary tetanus prevention is to give three doses of tetanus vaccine 1 month apart with additional boosters every 10 years for all individuals over 10 years of age. Individuals diagnosed with tetanus are also given three doses of anti-tetanus vaccines. Guidelines on tetanus vaccination do not include confirmation of immunity by antibody titer determination.
After inoculation, C. tetani transforms into a vegetative rod-shaped bacterium and produces the metalloprotease tetanospasmin (tetanus toxin) and tetanolysin. After reaching the spinal cord and brainstem via retrograde axonal transport 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 neuro-exocytosis. The net effect is inactivation of inhibitory neurotransmission that normally modulates anterior horn cells and muscle contraction. This disinhibition of anterior horn cells and autonomic neurons results in increased muscle tone, painful spasms, and widespread autonomic instability. Muscular rigidity in tetanus occurs though a complex mechanism that involves an increase in the resting firing rate of disinhibited motor neurons and lack of inhibition of reflex motor responses to afferent sensory stimuli. Lack of neural control of adrenal release of catecholamines induced by tetanus toxin produces a hyper-sympathetic state that manifests as sweating, tachycardia, and hypertension. Tetanus toxin-induced effects on anterior horn cells, the brainstem, and autonomic neurons are long lasting because recovery requires the growth of new axonal nerve terminals. This explains why only supportive care is offered to tetanus patients. Tetanolysin on the other hand has hemolytic properties and causes membrane damage in other cells, but its role in clinical tetanus is uncertain.
Eradication of C. tetani will reduce or even eliminate the vegetative cells that are the source of the toxin. Appropriate antibiotic therapy is therefore a necessary component in the treatment of tetanus. Several studies confirmed in vitro susceptibility of C. tetani topenicillins, metronidazole, cephalosporins, macrolides, and tetracyclines., We opted for metronidazole and ceftriaxone because they will offer a broad spectrum for antibacterial activity against many bacteria pending the outcome of sensitivity results from the wound swab taken, the medications were readily available and affordable to the patient as the relations complained bitterly of paucity of funds to even do the most basic of investigations. The bacteria (K. pneumoniae and P. aeruginosa) isolated from the swab microscopy test also showed sensitivity to ceftriaxone and was thus continued. The caregiver attitude of not providing prescribed medications on time might have contributed to the dismal outcome of this disease in this patient.
The presumed site of infection must be treated adequately to prevent relapse or recurrence. This can be a challenge in cancer patients presenting with difficult-to-treat chronic wounds. Proper treatment of the probable site of infection in our patient, even though readily accessible, had been a challenge because of its extensive nature, and surgical intervention was withheld for fear of provoking tumor bleeding and seedling, thus all that could be done was careful daily cleaning to reduce the population of the bacteria flora in the wound. In fact, some studies showed that despite treatment with high doses of penicillin, C. tetani was isolated after 16 days of intravenous penicillin in two cases. These data show that the intravenous route for penicillin may be inadequate for clearing the infection and emphasizes wound debridement in the treatment of tetanus.,
Many agents, alone and in combination, have been used to treat the muscle spasms of tetanus, which are painful and may threaten ventilation by causing laryngospasm or sustained contraction of the diaphragm. The ideal therapeutic regimen will abolish spasms without causing oversedation or hypoventilation. Benzodiazepines have emerged as the mainstay of symptomatic therapy for tetanus. This informed our choice of using diazepam via the intravenous route and the dose titrated as necessary to achieve sedation without respiratory depression. Moreover, 20 mg every 6 h effectively achieved these end points in this patient. Continuous intravenous infusion of diazepam is sometimes used for severe and intractable spasms in some patients with tetanus., The use of botulinum toxin against tetanus-induced spasms had also been advocated by some experts, but this is not in widespread use because of concerns on availability and allergic reactions.
Patient's monitoring and provision of respiratory support is of utmost importance in tetanus patients. Tetanic spasms sometimes demand that the airway be secured before other lines of therapy are possible. Intubation or tracheostomy, with or without mechanical ventilation, may be required for hypoventilation due to oversedation or laryngospasm or for the avoidance of aspiration by patients with trismus, disordered swallowing, or dysphagia. The need for these procedures should be anticipated, and they should be undertaken electively and early. This informed our decision for our patient to have a tracheostomy tube inserted for her from the onset so that any respiratory depression from the sedation can be tackled more easily. Other supportive care rendered were intravenous fluid administration, deep vein thrombosis prophylaxis with heparin, and nutritional support.
Despite all these interventions, our patient died after 5 days on admission from ventricular fibrillation, and this may probably be due to overactivity of the autonomic nervous system. Attempts at reversing this complication with magnesium sulfate and other supportive care were unsuccessful. The severity of spasms, duration of hospital stay, incubation period, onset time, immunization status, and socioeconomic background and the type of initial care are documented factors that affect mortality. Prognosis has become progressively more favorable in developed countries where mortality rate of mild and moderate tetanus in Western countries is presently about 6%. Critical care services are often unavailable or rudimentary in many developing countries (including the facility this patient was managed) and may contribute to the high mortality in our environment with case fatalities of up to 50%.,
| Conclusion|| |
Tetanus, a disease that is largely preventable by immunization, is still common in our environment and a major cause of morbidity and mortality. Clinical awareness by the attending physician, timely treatment, and proper tetanus vaccination before surgical excision, debridement, or cytotoxic chemotherapy on our cancer patients might be necessary to prevent this catastrophe. Further large and well-designed studies are essential to ascertain the benefit of active immunization against tetanus among cancer patients with chronic and fungating tumors.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
| References|| |
Bleck TP. Clostridium tetatni (tetanus). In: Mandell GL, Bennett JE, Dolin R, editors. Mandell, Douglas and Bennett's Principles and Practice of Infectious Diseases. 6th
ed. Philadelphia: Churchill Livingstone; 2004. p. 2817-22.
Thwaites CL, Farrar JJ. Preventing and treating tetanus: The challenge continues in the face of neglect and lack of research. BMJ 2003;326:117-8.
Anonymous. Validation of neonatal tetanus elimination in Andhra Pradesh, India. Wkly Epidemiol Rec 2004;79:292-7.
Talabi OA. A 3-year review of neurologic admissions in University College Hospital, Ibadan, Nigeria. West Afr J Med 2003;22:150-1.
Illis LS, Taylor FM. Neurological and electroencephalographic sequelae of tetanus. Lancet 1971;1:826-30.
Cook TM, Protheroe RT, Handel JM. Tetanus: A review of literature. Br J Anaesth 2001;87:477-87.
Ogunrin OA. Tetanus – A review of current concept in management. J Postgraduate Med 2009;11:46-61.
World Health Organization. The Immunological Basis for Immunization Series Module 3: Tetanus. 1993. p. 1-21.
Yamashita S, Karashima R, Tsushima A, Tawara S, Kawahara K. Tetanus caused by ulcerated giant phylloides tumor. Breast J 2007;13:614-5.
Texier S, Dermu M. Tetanus in a man presenting with a chronic wound. Presse Med 2004;33:759-60.
Reiche EMV, Nunes SOV, Morimoto HK. Stress, depression, the immune system, and cancer. Lancet Oncol 2004;5:617-25.
Gergen PJ, McQuillan GM, Kiely M, Ezzati-Rice TM, Sutter RW, Virella G, et al
. A population-based serologic survey of immunity to tetanus in the United States. N Eng J Med 1995;332:761-66.
Sanders RK. The management of tetanus 1996. Trop Doct 1996;26:107-15.
Lindley-Jones M, Lewis D, Southgate JL. Recurrent tetanus. Lancet 2004;363:2048.
Wickramasinghe SY, Fernando M. Recurrent tetanus. Br Med J 1967;4:530.
Opravil M, Fierz W, Matter L, Blaser J, Luthy R. Poor antibody response after tetanus and pneumococcal vaccination in immunocompromised, HIV-infected patients. Clin Exp Immunol 1991;84:185-9.
Miranda Filho DB, Ximenes RAA, Vaz VL, Viera AG, Albuquerque VMG. Randomized control trial of tetanus treatment with antitetanus immunoglobulin by the intrathecal or intramuscular route. Br Med J 2004;328:615-7.
List WF. The immediate treatment of tetanus with high doses of human tetanus antitoxin. Notfallmedizin 1981;7:731-3.
Rogers LC, Frykberg RG. Tetanus prophylaxis for diabetic foot ulcers. Clin Podiatr Med Surg 2006;23:769-75.
Lalli G, Bohnert S, Deinhardt K, Verastegui C, Schiavo G. The journey of tetanus and botulinum neurotoxins in neurons. Trends Microbiol 2003;11:431-7.
Campbell JL, Lam TM, Huynh TL, To SD, Tran TT, Nguyen VM, et al
. Microbiological characterization of Clostridium tetani
isolated from wounds of patients with clinically diagnosed tetanus. Am J Trop Med Hyg 2009;80:827-31.
Ahmadsyah I, Salim A. Treatment of tetanus: An open study to compare the efficacy of procain penicillin and metronidazole. Br Med J 1985;291:648-50.
Ismoedijanto M, Nassiruddin M, Prajitno BW. Case report: Diazepam in severe tetanus treatment. Southeast Asian J Trop Med Public Health 2004;35:175-80.
Rodrigo C, Fernando D, Rajapakse S. Pharmacological management of tetanus: An evidencebased review. Crit Care 2014;18:217.
Odia OJ, Njoku CH. Management of adult tetanus: A 5-year experience with the use of continuous infusion of diazepam and methocarbamol. Orient J Med 1991;3:142-5.
Hassel B. Tetanus: Pathophysiology, treatment, and the possibility of using botulinum toxin against tetanus-induced rigidity and spasms. Toxins (Basel) 2013;5:73-83.
Lipman J, James MF, Erskine J, Plit ML, Eidelman J, Esser JD. Autonomic dysfunction in severe tetanus: Magnesium sulfate as an adjunct to deep sedation. Crit Care Med 1987;15:987-8.
Ogunrin OA, Unuigbe EI. Tetanus: An analysis of the prognosticating factors of cases seen in a tertiary hospital in a developing African country between 1990 and 2000. Trop Doct 2004;34:240-41.
Trujillo MH, Castillo A, Espana J, Zerpa R. Impact of intensive care management on the prognosis of tetanus. Analysis of 641 cases. Chest 1987;92:63-5.
Afshar M, Raju M, Ansell D, Bleck TP. Narrative review: Tetanus-a health threat after natural disasters in developing countries. Ann Intern Med 2011;154:329-35.
Thwaites CL, Beeching NJ, Newton CR. Maternal and neonatal tetanus. Lancet 2015;385:362-70.