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Pathology of Diphtheria

Dr Sampurna Roy MD

 

                                                                                                                      

 

 

Diphtheria is an acute disease that results from a localized infection and a systemic toxemia caused by exotoxin producing strains of Corynebacterium diphtheriae.

The name is derived from the Greek words koryne (club) and diphtheria (leather), the latter referring to the grey membrane at the site of infection.

It is possible to completely eradicate Diphtheria by routine immunization with diphtheria toxoid.

Even in medically advanced countries, however, diphtheria may occur when immunization procedures breakdown because of war or complacency. 

An important epidemic occurred in Texus in 1970.

The low-grade endemicity of diphtheria depends on the occurrence of toxigenic Corynebacterium diphtheriae in the nasopharynges of a small number (fewer than 1%) of asymptomatic human carriers.

Transmission to nonimmune individuals usually occurs by the respiratory route.

IIn diphtheria, unlike food poisoning or tetanus, a parasitic relationship exists between the causative microorganism, Corynebacterium diphtheriae, and its host. 

Clinical Presentation:

Diphtheria is a composite of a local inflammation and a systemic intoxication.

Toxin produced locally by toxogenic strains of Corynebacterium diphtheriae is responsible for an inflammatory reaction on body surface at the site of infection (usually the oral pharynx, from which the process often extends to the nose or larynx).

Occasionally the tracheal, esophageal, or gastric mucosa is involved as well.

Less commonly, but particularly in the tropics, cutaneous trauma or burns may be the site of diphtheria.

The umbilical cord (in diphtheria neonatorum), the genital tract, and the conjuctivae are rare sites.

Unlike streptococcal tonsilitis, diphtheria is often insidious in onset and may be preceded by 2 to 3 days of listlessness, malaise, and headache before local symptoms occur.

Cervical adenopathy seems out of proportion to the pharyngeal lesion.

Soon small gray or white patches of exudates appear on  the pharyngeal mucosa, usually over the tonsils.

These enlarge and coalesce and, with the accumulation of blood, become gray or black.

This exudate constitutes the characteristic diphtheritic membrane, which consists of leukocytes and numerous bacteria enmeshed in a dense network of fibrin.

The epithelial surface becomes necrotic and densely adherent to the overlying membrane. This adherence explains why raw bleeding points are exposed when the membrane is forcibly removed.

If particularly extensive cases, the local process may produce mechanical respiratory obstruction, stridor, and even asphyxiation.

The local inflammatory process and its mechanical consequences are less important in the evolution of diphtheria than is the profound toxemia that characterizes the infection.

Diphtheria toxin, produced by Corynebacterium diphtheriae in response to infection of that organism by a specific bacteriophage, is a potent inhibitor of cellular protein synthesis.

It is readily absorbed from the point of production into the blood stream, and its effects are noted in many organs and systems throughout the body.

Clinically, apparent weakness or paralysis of limbs is rare.

Neuropathic manifestations of diphtheria are usually temporary and disappear within 2 or 3 months if the  patient survives.

Organs involved:

Lymph Node:  The lymphoid tissues both in regional lymph nodes and systemically (as in the spleen) undergo hyperplasia with the development of prominent germinal centers that are often centrally necrotic.

Heart:    Cardiac Path Online

Diphtheria toxin is particularly toxic to the myocardium.

In the early stages, interstitial edema, cloudy swelling of myocardial fibers, and the accumulation of fine cytoplasmic granules of lipid are seen microscopically.

Later these changes become widespread and are more severe.

Myocardial fibers eventually undergo necrosis, and a focal interstitial myocarditis with exudation of mononuclear cells occurs.

Cardiac involvement, either acutely in the form of cardiovascular collapse or as an arrhythmia or more chronically in the form of congestive heart failure, is the most common threat to life in diphtheria.

Kidney: A nonspecific, nonsuppurative interstitial nephritis is frequent in diphtheria and is believed to be responsible for the proteinuria often observed.

The renal lesion usually resolves completely in patients who recover.

Liver:  The liver is characteristically enlarged, hepatocytes exhibit cloudy swelling and less commonly focal necrosis.

Nerves: Diphtherial toxin has a special affinity for peripheral nerves.

Toxic effects are manifested in degeneration or even destruction of myelin sheaths.

Axis cylinders undergo swelling and rarely necrosis.

The paralytic effects of diphtheritic neuropathy are often sharply localized.

Paralysis of the voluntary muscles of the palate may produce a peculiar nasal quality of the voice and a tendency to regurgitate fluids through the nose.

Hypopharynx:  Hypopharyngeal involvement may lead to aspiration pneumonia.

Eye:  Involvement of extraocular muscles may produce diplopia, and involvement of the ciliary body may result in defective visual accommodation.

 

 

Image1 Image2  ;  Image3  ;  Image4  ;  Image5  ; Image6 (Dr. Y Tsutsumi)

 

 

Further reading:

Emergence of an invasive clone of nontoxigenic Corynebacterium diphtheriae in the urban poor population of Vancouver, Canada.

Mapping and comprehensive analysis of the extracellular and cell surface proteome of the human pathogen Corynebacterium diphtheriae.

Predictors of outcome in patients with diphtheria receiving intensive care.

Infections with Corynebacterium diphtheriae: six years' experience at an inner London teaching hospital.

Clinical features and predictors of diphtheritic cardiomyopathy in Vietnamese children.

Diphtheria: the patch remains.

Diphtheritic myocarditis: clinical and laboratory parameters of prognosis and fatal outcome.

Atrioventricular block in a toxic child: do not forget diphtheria.

Nontoxigenic corynebacterium diphtheriae: an emerging pathogen in England and Wales?

Fulminant diphtheria myocarditis in an unvaccinated preschool child.

 

 

 

Dr Sampurna Roy  MD

Consultant  Histopathologist (Kolkata - India)


 

 

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