Forensic Sci Med Pathol DOI 10.1007/s12024-014-9623-y
LESSONS FROM THE MUSEUM
Diphtheria and lethal upper airway obstruction Philip Beh • Roger W. Byard
Accepted: 4 October 2014 Ó Springer Science+Business Media New York 2014
Case report A 7-year-old boy was admitted to hospital with a 6 day history of fever and a sore throat. Two days before admission he had developed respiratory distress with intercostal recession. Despite performance of a tracheostomy and ventilation he did not improve and died the following day. Throat cultures grew Corynebacterium diphtheria. At autopsy the major features were limited to the airways and lungs. As can be seen in Fig. 1 the opened upper airway was characterized by extensive and confluent mucosal ulceration with a tracheostomy wound anteriorly. The tonsils were covered by a firmly-adherent yellow-gray exudate (a pseudomembrane). The pseudomembrane had detached more distally and impacted in the lower trachea and bronchi, thus rendering the tracheostomy useless. The left lung was atelectatic and areas of pneumonic consolidation were present in the right upper lobe, with a one centimeter diameter abscess in the right middle lobe. The remainder of the autopsy was not commented on. Death was due to upper airway obstruction complicating diphtheria. P. Beh Department of Pathology, The University of Hong Kong, Hong Kong, China R. W. Byard School of Medical Sciences, The University of Adelaide, Frome Rd, Adelaide, SA 5000, Australia R. W. Byard (&) School of Health Sciences, Level 3 Medical School North Building, The University of Adelaide, Frome Road, Adelaide, SA 5005, Australia e-mail: [email protected]
The specimen is currently located in the museum of the Department of Pathology at the University of Hong Kong, Hong Kong, China—#3215.
Discussion Pathology museum specimens are not only an invaluable source of teaching material that can be utilized for many decades [1], but they also provide a timely reminder of certain ‘‘forgotten’’ diseases that may be once more on the increase [2]. In Western countries diphtheria is one such condition. It is caused by Corynebacterium diphtheria, a toxigenic bacteria that is found as a commensal within the pharynx. Human infection results from direct or droplet contact [3]. The disease was first called ‘‘la diphthe´rite’’ by Brettoneau in 1826 because of the leatherlike exudate that attaches to the oropharynx (Greek: leather = dipthera), although it had been recognized for many centuries before this [4]. It was also called the ‘‘strangling angel’’ of children, as the shape of the oropharyngeal pseudomembranes was thought to resemble that of angel wings [5], or ‘‘white throat’’ in Chinese medicine. Loeffler identified Corynebacterium diphtheria as the causative agent in 1884 [6]. Despite criticisms from anti-immunization lobby groups, death rates from diphtheria have fallen dramatically following the introduction of universal immunization programs. Improvements in standards of living and public health measures have also contributed significantly to the decline in the disease in recent years [5]. Historically, young children have been the most vulnerable group; although girls are more susceptible to infection, boys have a higher fatality rate due to their increased incidence of laryngeal involvement [4].
123
Forensic Sci Med Pathol
After contact, an incubation period of 2–5 days is followed by a low grade fever with a sore throat. The clinical and pathological features result from the effects of a potent toxin which causes a pseudomembrane to form, covering the soft palate, uvula, and tonsils after 24 h. The membrane is initially white but darkens as it is permeated by blood. A more severe form in younger children results in ‘‘bull neck’’ diphtheria due to swelling of the adjacent cervical lymph nodes and soft tissues, with compression of the jugular veins [4]. Necrosis of the oropharynx and infiltration of inflammatory cells into the underlying skeletal muscle may also occur, again with marked hemorrhage. Histologically the pseudomembranes may have an inner layer of fibrin and an outer layer of neutrophils containing aggregates of bacteria [3, 7]. Other findings at autopsy include myocardial pallor with dilated cardiac chambers that have a characteristic ‘‘streaky’’ appearance. Microscopic sections may show marked hyaline degeneration and necrosis with lipid vacuolization of surviving myocytes that are surrounded by a mononuclear cell infiltrate [3]. Examination of the gastrointestinal tract may reveal superficial gastric mucosal erosions. Other findings can include splenic abscesses, osteomyelitis, mycotic aneurysms, and septic arthritis [5]. Cases of diphtheria may come to forensic attention because of the potential for sudden and unexpected death. A variety of mechanisms may be responsible for a lethal outcome. As the reported case demonstrates, acute upper airway obstruction can result from dislodgement of the upper airway pseudomembranes with impaction more distally, resulting in critical airway obstruction. This is clearly illustrated in Fig. 1 of the reported case. Diphtheria is, however, not the only condition where acute upper airway obstruction can be caused by displaced pseudomembranes; for example lethal cases have been reported in infectious mononucleosis [8]. Many infected patients have cardiac involvement due to direct myotoxicity from the diphtheria toxin which may result in heart block or cardiac failure [4, 9]. Both myocarditis and endocarditis may also develop. The toxin can also damage anterior horn cells, dorsal root ganglia, and cranial nerves causing paralysis. Involvement of palatal muscles may cause regurgitation of swallowed fluids and aspiration, and respiratory failure may develop if the muscles of respiration are also damaged [10]. Other potentially lethal problems are renal failure, hypotension, disseminated intravascular coagulation, and endocrine failure due to adrenal gland involvement [9]. Although diphtheria may be regarded as a historical problem, outbreaks in a number of countries in recent times
123
Fig. 1 The specimen shows the opened upper airway of a 7-year-old boy extending from the tongue, through the larynx to the trachea and main bronchi. The attached lungs have been coronally sectioned. A vertical tracheostomy opening can be seen in the upper trachea above impacted desquamated material. The specimen is characterized by extensive and confluent mucosal ulceration with an attached exudate extending from the epiglottis to the main bronchi. Detachment of the diphtheric pseudomembrane has resulted in occlusion of the lower trachea (arrow) and proximal main bronchi causing lethal airway obstruction
have demonstrated that incomplete population immunity and population movements can render communities vulnerable. Recent travel to countries where the disease is endemic is another factor to be considered [11], as is the possibility of infection from asymptomatic carriers if they have not been immunized [12, 13]. Increasing international travel and refugee movements are issues to consider. For these reasons, as with a number of other ‘‘forgotten diseases,’’ forensic pathologists must remain vigilant for such cases, despite working in countries with good public health infrastructure, high standards of medical care, and established immunization programs.
Forensic Sci Med Pathol
References 1. Byard RW. The use of archival tissues, organs and pathology museums—‘‘mortui vivos docent’’ (let the dead teach the living). Forensic Sci Med Pathol. 2007;3:175–6. 2. Byard RW. An analysis of possible mechanisms of unexpected death occurring in hydatid disease (echinococcosis). J Forensic Sci. 2009;54:919–22. 3. Hadfield TL, McEvoy P, Polotsky Y, Tzinserling VA, Yakovlev AA. The pathology of diphtheria. J Infect Dis. 2000;181(Suppl):S116–20. 4. Hodes HL. Diphtheria. Pediatr Clin Nth Am. 1979;26:445–59. 5. Byard RW. Diphtheria—‘The Strangling Angel’ of children. J Forensic Leg Med. 2013;20:65–8. 6. Hart PE, Lee PYC, Macallan DC, Wansbrough-Jones MH. Cutaneous and pharyngeal diphtheria imported from the Indian subcontinent. Postgrad Med. 1996;72:619–20. 7. Byard RW. Sudden death in the young. 3rd ed. Cambridge, UK: Cambridge University Press; 2010. p. 194.
8. Byard RW. Unexpected death due to infectious mononucleosis. J Forensic Sci. 2002;47:202–4. 9. Jenkins IA, Saunders M. Infections of the airway. Pediatr Anesthes. 2009;19(Suppl 1):118–30. 10. Bowler DP. Post-diphtheritic polyneuritis with respiratory paralysis. Med J Aust. 1960;47:733–4. 11. Wagner KS, White JM, Crowcroft NS, De Martin S, Mann G, Efstratiou A. Diphtheria in the United Kingdom, 1986–2008: the increasing role of Corynebacterium ulcerans. Epidemiol Infect. 2010;138:1519–30. 12. Lumio J, Suomalainen P, Olander RM, Saxe´n H, Salo E. Fatal case of diphtheria in an unvaccinated infant in Finland. Pediatr Infect Dis. 2003;22:844–6. 13. Farizo KM, Strebel PM, Chen RT, Kimbler A, Cleary TJ, Cochi SL. Fatal respiratory disease due to Corynebacterium diphtheriae: case report and review of guidelines for management, investigation, and control. Clin Infect Dis. 1993;16:59–68.
123
LESSONS FROM THE MUSEUM
Diphtheria and lethal upper airway obstruction Philip Beh • Roger W. Byard
Accepted: 4 October 2014 Ó Springer Science+Business Media New York 2014
Case report A 7-year-old boy was admitted to hospital with a 6 day history of fever and a sore throat. Two days before admission he had developed respiratory distress with intercostal recession. Despite performance of a tracheostomy and ventilation he did not improve and died the following day. Throat cultures grew Corynebacterium diphtheria. At autopsy the major features were limited to the airways and lungs. As can be seen in Fig. 1 the opened upper airway was characterized by extensive and confluent mucosal ulceration with a tracheostomy wound anteriorly. The tonsils were covered by a firmly-adherent yellow-gray exudate (a pseudomembrane). The pseudomembrane had detached more distally and impacted in the lower trachea and bronchi, thus rendering the tracheostomy useless. The left lung was atelectatic and areas of pneumonic consolidation were present in the right upper lobe, with a one centimeter diameter abscess in the right middle lobe. The remainder of the autopsy was not commented on. Death was due to upper airway obstruction complicating diphtheria. P. Beh Department of Pathology, The University of Hong Kong, Hong Kong, China R. W. Byard School of Medical Sciences, The University of Adelaide, Frome Rd, Adelaide, SA 5000, Australia R. W. Byard (&) School of Health Sciences, Level 3 Medical School North Building, The University of Adelaide, Frome Road, Adelaide, SA 5005, Australia e-mail: [email protected]
The specimen is currently located in the museum of the Department of Pathology at the University of Hong Kong, Hong Kong, China—#3215.
Discussion Pathology museum specimens are not only an invaluable source of teaching material that can be utilized for many decades [1], but they also provide a timely reminder of certain ‘‘forgotten’’ diseases that may be once more on the increase [2]. In Western countries diphtheria is one such condition. It is caused by Corynebacterium diphtheria, a toxigenic bacteria that is found as a commensal within the pharynx. Human infection results from direct or droplet contact [3]. The disease was first called ‘‘la diphthe´rite’’ by Brettoneau in 1826 because of the leatherlike exudate that attaches to the oropharynx (Greek: leather = dipthera), although it had been recognized for many centuries before this [4]. It was also called the ‘‘strangling angel’’ of children, as the shape of the oropharyngeal pseudomembranes was thought to resemble that of angel wings [5], or ‘‘white throat’’ in Chinese medicine. Loeffler identified Corynebacterium diphtheria as the causative agent in 1884 [6]. Despite criticisms from anti-immunization lobby groups, death rates from diphtheria have fallen dramatically following the introduction of universal immunization programs. Improvements in standards of living and public health measures have also contributed significantly to the decline in the disease in recent years [5]. Historically, young children have been the most vulnerable group; although girls are more susceptible to infection, boys have a higher fatality rate due to their increased incidence of laryngeal involvement [4].
123
Forensic Sci Med Pathol
After contact, an incubation period of 2–5 days is followed by a low grade fever with a sore throat. The clinical and pathological features result from the effects of a potent toxin which causes a pseudomembrane to form, covering the soft palate, uvula, and tonsils after 24 h. The membrane is initially white but darkens as it is permeated by blood. A more severe form in younger children results in ‘‘bull neck’’ diphtheria due to swelling of the adjacent cervical lymph nodes and soft tissues, with compression of the jugular veins [4]. Necrosis of the oropharynx and infiltration of inflammatory cells into the underlying skeletal muscle may also occur, again with marked hemorrhage. Histologically the pseudomembranes may have an inner layer of fibrin and an outer layer of neutrophils containing aggregates of bacteria [3, 7]. Other findings at autopsy include myocardial pallor with dilated cardiac chambers that have a characteristic ‘‘streaky’’ appearance. Microscopic sections may show marked hyaline degeneration and necrosis with lipid vacuolization of surviving myocytes that are surrounded by a mononuclear cell infiltrate [3]. Examination of the gastrointestinal tract may reveal superficial gastric mucosal erosions. Other findings can include splenic abscesses, osteomyelitis, mycotic aneurysms, and septic arthritis [5]. Cases of diphtheria may come to forensic attention because of the potential for sudden and unexpected death. A variety of mechanisms may be responsible for a lethal outcome. As the reported case demonstrates, acute upper airway obstruction can result from dislodgement of the upper airway pseudomembranes with impaction more distally, resulting in critical airway obstruction. This is clearly illustrated in Fig. 1 of the reported case. Diphtheria is, however, not the only condition where acute upper airway obstruction can be caused by displaced pseudomembranes; for example lethal cases have been reported in infectious mononucleosis [8]. Many infected patients have cardiac involvement due to direct myotoxicity from the diphtheria toxin which may result in heart block or cardiac failure [4, 9]. Both myocarditis and endocarditis may also develop. The toxin can also damage anterior horn cells, dorsal root ganglia, and cranial nerves causing paralysis. Involvement of palatal muscles may cause regurgitation of swallowed fluids and aspiration, and respiratory failure may develop if the muscles of respiration are also damaged [10]. Other potentially lethal problems are renal failure, hypotension, disseminated intravascular coagulation, and endocrine failure due to adrenal gland involvement [9]. Although diphtheria may be regarded as a historical problem, outbreaks in a number of countries in recent times
123
Fig. 1 The specimen shows the opened upper airway of a 7-year-old boy extending from the tongue, through the larynx to the trachea and main bronchi. The attached lungs have been coronally sectioned. A vertical tracheostomy opening can be seen in the upper trachea above impacted desquamated material. The specimen is characterized by extensive and confluent mucosal ulceration with an attached exudate extending from the epiglottis to the main bronchi. Detachment of the diphtheric pseudomembrane has resulted in occlusion of the lower trachea (arrow) and proximal main bronchi causing lethal airway obstruction
have demonstrated that incomplete population immunity and population movements can render communities vulnerable. Recent travel to countries where the disease is endemic is another factor to be considered [11], as is the possibility of infection from asymptomatic carriers if they have not been immunized [12, 13]. Increasing international travel and refugee movements are issues to consider. For these reasons, as with a number of other ‘‘forgotten diseases,’’ forensic pathologists must remain vigilant for such cases, despite working in countries with good public health infrastructure, high standards of medical care, and established immunization programs.
Forensic Sci Med Pathol
References 1. Byard RW. The use of archival tissues, organs and pathology museums—‘‘mortui vivos docent’’ (let the dead teach the living). Forensic Sci Med Pathol. 2007;3:175–6. 2. Byard RW. An analysis of possible mechanisms of unexpected death occurring in hydatid disease (echinococcosis). J Forensic Sci. 2009;54:919–22. 3. Hadfield TL, McEvoy P, Polotsky Y, Tzinserling VA, Yakovlev AA. The pathology of diphtheria. J Infect Dis. 2000;181(Suppl):S116–20. 4. Hodes HL. Diphtheria. Pediatr Clin Nth Am. 1979;26:445–59. 5. Byard RW. Diphtheria—‘The Strangling Angel’ of children. J Forensic Leg Med. 2013;20:65–8. 6. Hart PE, Lee PYC, Macallan DC, Wansbrough-Jones MH. Cutaneous and pharyngeal diphtheria imported from the Indian subcontinent. Postgrad Med. 1996;72:619–20. 7. Byard RW. Sudden death in the young. 3rd ed. Cambridge, UK: Cambridge University Press; 2010. p. 194.
8. Byard RW. Unexpected death due to infectious mononucleosis. J Forensic Sci. 2002;47:202–4. 9. Jenkins IA, Saunders M. Infections of the airway. Pediatr Anesthes. 2009;19(Suppl 1):118–30. 10. Bowler DP. Post-diphtheritic polyneuritis with respiratory paralysis. Med J Aust. 1960;47:733–4. 11. Wagner KS, White JM, Crowcroft NS, De Martin S, Mann G, Efstratiou A. Diphtheria in the United Kingdom, 1986–2008: the increasing role of Corynebacterium ulcerans. Epidemiol Infect. 2010;138:1519–30. 12. Lumio J, Suomalainen P, Olander RM, Saxe´n H, Salo E. Fatal case of diphtheria in an unvaccinated infant in Finland. Pediatr Infect Dis. 2003;22:844–6. 13. Farizo KM, Strebel PM, Chen RT, Kimbler A, Cleary TJ, Cochi SL. Fatal respiratory disease due to Corynebacterium diphtheriae: case report and review of guidelines for management, investigation, and control. Clin Infect Dis. 1993;16:59–68.
123
