Journal of Forensic and Legal Medicine 20 (2013) 65e68

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Journal of Forensic and Legal Medicine

j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / j fl m

Review

Diphtheria e ‘The strangling angel’ of children

Roger W. Byard, MD, Forensic pathologist *
School of Medical Sciences, The University of Adelaide, Level 3 Medical School North Building, Frome Rd, Adelaide, 5005 South Australia, Australia

a r t i c l e i n f o a b s t r a c t

Article history: Diphtheria, an acute infectious condition caused by Corynebacterium diphtheriae, was once a major killer
Received 12 February 2012 of children. Although the mortality rates dropped dramatically in the mid-twentieth century, due to
Accepted 20 April 2012 a combination of improved standards of living and immunization programs, outbreaks are still occurring.
Available online 24 May 2012
Two children, aged four and five years respectively, are reported to demonstrate characteristic features of
lethal cases. Death in case 1 was due to an extensive upper airway pseudomembrane causing acute
Keywords:
respiratory failure. The diagnosis of diphtheria was only made at postmortem. Death in case 2 was due to
Forensic
acute cardiac failure with heart block complicating diphtheria. Other mechanisms in fatal cases involve
Diphtheria
Childhood death
disseminated intravascular coagulation, renal and endocrine failure. Declining levels of immunity among
Airway obstruction adults has resulted in a change in the epidemiological pattern of the disease with an older age of victims
in recent outbreaks. As a result of population shifts and failure to immunize children it is likely that
forensic pathologists may see more cases of diphtheria in the future. Due to the rarity of cases in Western
communities and atypical presentations, the diagnosis may only be established at autopsy.
Ó 2012 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

1. Introduction 2. Case reports

Diphtheria is an acute infectious condition caused by Coryne- The pathology archives at The University of Adelaide, Australia,
bacterium diphtheriae, a toxigenic bacteria that lives as were searched for cases of lethal diphtheria. Two autopsy cases
a commensal in the human pharynx. It was once a major killer of were located, the details of which are reported below.
children occurring in epidemics that resulted in thousands of Case 1: A four-year-old girl was admitted to hospital with a sore
deaths.1 The mortality rates began to drop in the twentieth century throat and respiratory distress. The presence of an exudate over her
in countries where standards of living improved, and then tonsils raised the possibility of diphtheria however microbiological
dramatically fell once immunization programs were introduced.1 cultures do not reveal C. diphtheriae. Despite antiobiotic therapy she
However, despite these events it remains a significant pathogen died within 24 h of admission “in acute respiratory distress”.
in many parts of the world, even today. At autopsy the most striking findings were in the upper airway
Death occurs from a variety of mechanisms, however the name where yellow adherent material was present in the pharynx
‘strangling angel’ of children arose from the wing shaped pseudo- covering the tonsils. This was associated with cervical lymphade-
membranes that form in the oropharynx. Dislodgment and impac- nopathy and a pseudomembrane which extended from the
tion of these pseudomembranes caused acute airway obstruction epiglottis throughout the entire larynx into the trachea and bronchi
and sudden death.1,2 Given that there has been a resurgence of cases (Fig. 1). Histology showed desquamation of lining epithelium in the
of non-lethal and lethal diphtheria in a number of countries in recent upper airway with extensive fibrinopurulent debris. Cervical lymph
decades, and that considerable population displacements are nodes were congested with necrotic germinal centers and the lungs
occurring due to refugee and immigration movements, more cases were oedematous and haemorrhagic. A postmortem nasal swab
may be encountered in forensic practice. The following review was grew Corynebacterium diphtheria. Death was due to acute respira-
undertaken, therefore, to highlight the pathological features of this tory failure complicating diphtheria. [Further images, but not
‘forgotten’ disease. To illustrate lethal manifestations in children two pathological details, of this case have been published previously3].
cases are also described. Case 2: A five-year-old boy was admitted to hospital, ill with
a sore throat. A grey membrane was present over his tonsils and the
adjacent pharynx and C. diphtheriae was isolated on cultures. He
was treated with antibiotics and diphtheria antitoxin but devel-
* Tel.: þ61 8 8303 5441; fax: þ61 8 8303 4408.
E-mail address: [email protected]. oped respiratory distress secondary to pseudomembrane formation

1752-928X/$ e see front matter Ó 2012 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.
doi:10.1016/j.jflm.2012.04.006
66 R.W. Byard / Journal of Forensic and Legal Medicine 20 (2013) 65e68

Dramatic declines in the incidence of diphtheria occurred

following mass immunization campaigns in Western countries
instituted in the 1940s and 1950s, although improved economic
and living conditions (with smaller families and less crowding) had
already led to a decline in numbers. For example, in Cracow, Poland
between 1889 and 1909 the percentage of case of diphtheria in
children under five years of age was 76%. This reduced to 43%
between 1930 and 1932 without immunization campaigns.6 The
rate of diphtheria in Baltimore, US, in 1900 was 260 per 100,000,
124 per 100,000 in 1925 and 0 per 100,000 in 1960.1 Transmission
occurs by direct contact or by droplet infection from sneezing or
coughing.9

3.2. Pathological effects

The pathogical consequences of diphtheria infection are caused

by production of a potent toxin. The incubation period may be from
one to eight days, but is usually between two to five days. The onset is
often nonspecific with a lowgrade fever and a sore throat which may
mimic streptococcal pharyngitis, candidiasis or infectious mono-
nucleosis.1,10,11 After about 24 h the pseudomembrane appears
covering the soft palate, uvula and tonsils. This initially appears
white but darkens as blood seeps into it. In young children a more
severe form occurs known as malignant or “bull neck” diphtheria.
The onset is abrupt and the growth of the pseudomembrane more
rapid with involvement of the buccal cavity, entire pharynx, middle
ear and nose.1 The soft palate, uvula and tonsils may undergo
necrosis and slough, and necrotic lesions may penetrate into the
underlying skeletal muscle with marked hemorrhage.9 More distal
airway may have thinner pseudomembranes and the lungs are
hemorrhagic and edematous.12 Pseudomembranes may have an
inner layer of fibrin with an outer coating of neutrophils with
aggregates of embedded bacteria within the necrotic material.9
There is marked swelling of the cervical lymph nodes and
adjacent soft tissues producing the characteristic “bull neck”
appearance. Compression of the jugular veins may cause marked
Fig. 1. Lung with an opened bronchus showing pseudomembranous occlusion (arrow)
in a four-year old girl with diphtheria who died of acute respiratory distress. congestion of the face.1 Other parts of the upper airway may be
involved with nasal and laryngeal diphtheria, the latter associated
with a high mortality rate.
The heart may have pale, dilated, chambers with a characteristic
and required a tracheostomy with ventilation. He then developed
‘streaky” appearance. Histologic sections may show marked hyaline
complete atrioventricular dissocation with right bundle branch
degeneration and necrosis with mononuclear cell infiltration and
block, but remained clinically stable. He died suddenly in the
lipid vacuoles within surviving myocytes.9 Adequate treatment
twelfth hospital day.
requires rapid administration of diphtheria antitoxin and antibiotic
At autopsy there was evidence of cardiac failure with a pale and
coverage.11 Superficial mucosal erosions may be present within the
markedly dilated heart and bilateral straw-coloured pleural effu-
stomach and non-lethal diphtherial infections of the skin are found
sions. The tonsils were inflamed but without pseudomembranes.
in the tropics, although these may lead to pharyngeal involvement
Death was due to acute cardiac failure complicating diphtheria.
through autoinfection.2 Other sites of infection involve mycotic
aneurysm formation, splenic abscess, osteomyelitis and septic
3. Discussion arthritis.4

3.1. Historical perspective 3.3. Lethal consequences

Diphtheria was first recognized as a specific disease by Bretto- Death may be quite sudden and unexpected resulting from
neau in 1826 and named “la diphthérite” because of the leather-like dislodgement or growth of pseudomembranes with acute
exudate that formed in the oropharynx (Greek: leather ¼ dipthera).1 obstruction of the upper airway as in case 1. Cardiac involvement
It was not until 1884 that Loeffler first identified Corynebacterium occurs with both endocarditis and myocarditis being reported.
diphtheria as the causative agent.4 At the time it was one of the most Almost 50% of infected patients have some degree of cardiac
serious of childhood infections with one in 20 individuals in impairment which has been shown in an animal model to be due to
temperate climates having had the disease, with a mortality rate of direct myotoxicity from the diphtheria toxin.1 This may cause lethal
5e10%.5 Seventy percent of those infected were aged less than 15 heart block or cardiac failure13 and may take a number of days to
years.6 Rural communities were the most vulnerable. In the 16th and develop, as in case 2. Those with the most severe form of the
17th centuries in Spain diphtheria had been known as “morbus disease develop myocarditis within the first few days of the illness.1
suffocans” or “garotillo”7 and in the 18th century in the New England Endocarditis most often involves non toxigenic strains and is
states of the US as “throat distemper”.8 associated with prosthetic valves or homografts.4,14,15
 R.W. Byard / Journal of Forensic and Legal Medicine 20 (2013) 65e68 67

Diphtheria toxin also damages neural structures such as the products, but which recently has been associated with domestic
anterior horn cells, dorsal root ganglia and cranial nerves with cats and dogs.20e22
resultant paralysis, most often involving the palatal muscles. This
may predispose to regurgitation of swallowed fluids through the
nose9 and aspiration from bulbar paralysis. Involvement of the 4. Conclusion
muscles of respiration may cause respiratory failure.16 All of the
pathological effects of diphtheria have been reproduced in animal Recent outbreaks of diphtheria in a range of countries have
models by injecting the toxin.1 demonstrated that incomplete population immunity and pop-
The mortality rate of diphtheria varies depending on age and ulation movements may render communities vulnerable to this
sex, with young children historically being the most vulnerable. uncommon infection. As a result of population shifts and failure to
Girls are more susceptible to infection, however the fatality rate in immunize children it is likely that forensic pathologists may see
boys is higher mostly due to their higher incidence of laryngeal more cases of diphtheria in the future. Due to the rarity of cases in
involvement.1 Other problems that may lead to death are dissem- Western communities, and atypical presentations, the diagnosis
inated intravascular coagulation, renal failure, and hypotension and may only be established at autopsy, as in case 1.23 A high index of
endocrine failure associated with adrenal gland involvement13 suspicion needs to be maintained, therefore, in assessing possible
(Table 1). cases so that forensic facilities are able to quickly inform public
health authorities. This report demonstrates the range of mani-
festations that infections with C. diphtheria may have, possible
3.4. Epidemiology lethal mechanisms that may lead to sudden and unexpected death,
and recent changes in the epidemiology. The autopsy in suspected
Diphtheria is vulnerable to elimination, as humans are the only cases should include microbiological samples from the oropharynx
reservoir, an effective vaccine exists and the seasonal incidence aids and upper airway, in addition to extensive histological sampling of
interruption of its transmission, but unfortunately eradication has cardiac, neural, upper airway and lymphoid lesions.
not occurred.7 The incidence and rate of diphtheria epidemics has
varied between developed and developing countries, with the Conflicts of interest
latter rarely having large scale outbreaks in the past.6 This was None declared.
considered due to the high rate of C. diphtheria skin infections
which led to the development of early immunity. This situation has, Funding
however changed in recent years with outbreaks reported in None declared.
several countries associated with high mortality rates involving
older victims. For example, in Khartoum, Sudan, 50% of cases Ethical approval
admitted to hospital in an outbreak in 1978 (pre-immunization None declared.
programs) were children under the age of five years. This con-
trasted with an outbreak in 1988 when only 19% were under five
years. Similar trends have been reported in Jordan, Algeria and References
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