Etiology and pathogenesis
The causative agent of the disease is Corynebacterium diphtheriae. It is an aerobic, Gram-positive, spore-forming bacterium. In the current epidemiological situation, the aggressive biovar gravis is most commonly encountered. The bacterium is extremely resistant in the external environment: on toys and door handles (in droplets of saliva or pieces of membranes) it can survive for up to 15 days, in water for up to 20 days, and in dust for up to 40 days. Direct sunlight and high temperatures are lethal to it (it is killed instantly by boiling).
Transmission occurs via airborne droplets or by contact from an infected person. The bacterium itself does not penetrate deep into tissues, multiplying instead on the surface of mucous membranes or in areas of skin damage. The primary threat is diphtheria exotoxin (a 62 kDa polypeptide).
The action of the pathogen is divided into local and systemic:
- Local: Aggression enzymes (hyaluronidase, fibrinolysin) destroy the extracellular matrix. The toxin causes superficial epithelial necrosis and paralytic vasodilation. Capillary permeability increases, leading to the leakage of exudate containing fibrinogen. Fibrinogen clots, forming a dense fibrinous membrane tightly adhered to the tissues.
- Systemic: The exotoxin is absorbed into the bloodstream, blocking protein synthesis in cells. This leads to severe damage (necrosis and demyelination) in the myocardium, nerve trunks, kidneys, and adrenal glands.
Clinical presentation
The incubation period lasts from 1 to 6 days. The most frequent localization of the primary focus is the oropharynx and tonsils. An important feature of the disease is clinical dissociation: the patient exhibits pronounced intoxication syndrome (weakness, pallor), yet fever remains subfebrile or moderate, and typical catarrhal symptoms (runny nose, cough) are mild.
Local mucosal manifestations: A characteristic coating (pseudomembrane) forms on the tonsils. It has a gray-brown or white-gray color, a smooth surface, and a dense consistency. The membrane is firmly fused with the mucosa: if an attempt is made to remove it with a spatula, a bleeding surface is exposed.
In mild cases, the membranes do not extend beyond the tonsils. In the severe (toxic) form, the process spreads to the uvula, palatine arches, and soft palate. Massive lymphadenopathy and marked soft tissue edema of the neck develop—the so-called "bull neck" sign.
Diphtheritic croup (laryngeal involvement): The process leads to stenosis of the laryngeal lumen. It develops in stages:
- Progressive hoarseness progressing to complete aphonia.
- Rough, " barking" cough.
- Stenotic breathing with noisy inspiration and the use of accessory muscles.
Specific complications
The severity of diphtheria is largely determined by toxic complications, which can be fatal.
Toxic myocarditis: Occurs in 10–25% of patients. It most commonly manifests in the 2nd–3rd week of the illness, when local symptoms in the throat are already subsiding. Early development (in the 1st week) is prognostically extremely unfavorable. It presents with tachycardia, cardiac enlargement, conduction blocks, and ECG changes (PR prolongation, ST-T abnormalities). Blood AST enzyme levels correlate directly with the extent of myonecrosis.
Toxic neuropathy (polyneuropathy): The process is multiphasic:
- Early phase (week 2–3): Involvement of cranial nerves. Soft palate paresis occurs (nasal voice, choking on liquids).
- Autonomic dysfunction: Involvement of vasomotor centers leads to arterial hypotension.
- Late phase (week 5): Oculomotor nerves are affected (strabismus, accommodation disorders). Symmetric peripheral polyneuropathy develops with depressed reflexes and muscle weakness up to diaphragmatic paralysis. Clinically and in terms of cerebrospinal fluid composition, this condition is indistinguishable from Guillain-Barré syndrome.
Diagnostics and treatment
The basis of diagnosis is clinical presentation combined with epidemiological history. The main laboratory method is bacteriological culture of throat and nasal swabs on special media (e.g., Clauberg II medium) with mandatory determination of toxigenicity of the isolated strains. Direct smear microscopy is not recommended due to low reliability.
Hospitalization is strictly mandatory. If a severe form (myocarditis, neuropathy) is suspected, strict bed rest is prescribed for at least 3 weeks.
Specific antitoxic therapy: Administration of equine diphtheria antitoxin (DAT) is the only way to neutralize the toxin. In toxic forms, the serum is administered immediately without waiting for culture results (after performing a protein sensitivity test). Dosage ranges from 10,000 to 150,000 IU intramuscularly. The efficacy of the serum drops rapidly with each hour from the onset of the disease.
Antibacterial therapy: Used (aminopenicillins, macrolides) solely to clear the infection focus and prevent transmission to contacts. Antibiotics have no effect on the exotoxin circulating in the blood. Discharge is permitted only after two negative bacterial cultures (sampled 24 hours after discontinuing antibiotics).
Prevention
The basis of protection is routine vaccination with toxoids (DTaP, Td vaccines). Vaccination does not guarantee absolute protection against infection, but it is critically important: it reliably prevents the development of severe and toxic forms of the disease.
Immunity following diphtheria is unstable; therefore, recovered patients are also subject to routine vaccination. In an infection focus, contacts are monitored for 7 days. Mandatory bacteriological screening of all contacts (especially in children's groups) is performed to identify carriers. Carriers are prescribed erythromycin chemoprophylaxis.
To memorize the triad of diphtheritic croup, use the "H-B-S" rule: Hoarseness (progressing to aphonia), Barking cough, Stenotic breathing.
Class and exam questions
Why is it forbidden to attempt to remove the coating from the tonsils with a spatula in diphtheria?
The fibrinous membrane is tightly adhered to the underlying epithelium. Any attempt to remove it exposes a bleeding surface, which dramatically accelerates the absorption of the exotoxin into the systemic circulation.
Can diphtheria be cured with antibiotics alone?
No. Antibiotics eradicate the bacterium itself at the infection site but have no effect on the exotoxin already released into the blood. Administration of antitoxic serum is vital for neutralizing the toxin.
Should a child who has already had diphtheria be vaccinated against it?
Yes. Post-infection antitoxic immunity in diphtheria is unstable. Having had the disease does not serve as a medical exemption, and convalescents are subject to vaccination on a general basis.
What else to study on this topic
- Differential diagnosis of diphtheria with streptococcal pharyngitis and infectious mononucleosis
- Features of the clinical presentation of nasal diphtheria in young children
- Algorithm for performing the skin sensitivity test to horse protein before administering DAT
- Interpretation of serological diagnostic results (assessment of protective antibody titers)
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