Diphtheria: Symptoms, Complications, and Signs of Severity

Diphtheria is dangerous not only because of the local inflammation, but primarily because of the toxin, which attacks the heart, nerves, and respiratory tract. The severity of symptoms and the risk of complications largely depend on the extent of the local process and the speed of treatment. The most common severe complications are myocarditis and neuritis, as well as airway obstruction, especially in young children. The overall mortality rate, according to current data, is estimated at approximately 5-10 percent, higher in children under 5 years of age and adults over 40. [1]

The incubation period is typically 2-5 days, but can range from 1 to 10 days. The onset is often gradual: malaise, sore throat, loss of appetite, low-grade fever, then, after 2-3 days, a dense, gray or bluish-white film forms, tightly adherent to the mucous membrane and bleeding when removed. With severe intoxication, pallor, tachycardia, confusion, and, in severe cases, a "bull neck" due to soft tissue swelling appear. [2]

The clinical picture varies depending on the location of the infection. The oropharynx and tonsils are most commonly affected, while the larynx and nose are less commonly affected. Cutaneous and other non-respiratory forms exist. The cutaneous form is more common in the tropics and is less likely to cause systemic toxicity, but it is important as a potential reservoir for the pathogen. [3]

Even with partial vaccination, atypical and milder manifestations are possible, increasing the risk of diagnostic errors and late recognition. In a number of countries, health authority reports emphasize that the classic membrane does not always appear, and diphtheria can masquerade as common bacterial pharyngitis. This requires vigilance and the proper selection of samples for laboratory confirmation. [4]

How to recognize it at the start: clinical landmarks

The oropharyngeal form is characterized by gradual sore throat, low-grade fever, and the appearance of films on the tonsils and soft palate. The film is dense and fibrinous, causing bleeding when removed, and its spread correlates with the risk of toxic effects. Extensive films and pronounced swelling of the neck are markers of a severe course and possible early toxemia. [5]

In the laryngeal form, hoarseness, a barking cough, increasing inspiratory stridor, and the risk of rapid airway obstruction come to the fore. This is especially dangerous for children, where respiratory failure can develop more rapidly than in adults. [6]

The nasal form initially resembles rhinitis: mucopurulent discharge, later mixed with blood, and a localized thin film, often on the septum. Symptoms are usually milder, but confirmation is necessary, as the nasopharynx remains a source of transmission. [7]

The cutaneous form manifests as ulcers with sharp edges and a gray film or crust. It can persist and be associated with colonization by other bacteria, complicating the interpretation of smears. Systemic complications are less common than with the respiratory form, but laboratory testing for the toxigenicity of the strain is mandatory. [8]

Timeline of symptoms and complications

The first symptoms appear several days after infection, and membranes usually form by the second or third day of illness. In severe cases, deterioration can occur rapidly due to local obstruction and increasing intoxication. During this period, it is important to assess the voice, breathing, pulse, and degree of neck swelling. [9]

Myocarditis can occur early or weeks after the onset of the disease. It manifests as rhythm and conduction disturbances and signs of heart failure and is a leading cause of death. Early onset carries a poorer prognosis. [10]

Neuritis most often affects the motor nerves. Soft palate paralysis typically develops in the third week, while paresis of the ocular muscles, limbs, and diaphragm develops after the fifth week. If the diaphragm is affected, respiratory failure and aspiration pneumonia are possible. In most cases, neurological impairment is reversible over time. [11]

Infants and young children are more likely to develop life-threatening respiratory complications. Without treatment, carriage can persist for weeks, supporting transmission within families and communities. [12]

Table 1. Approximate timeline of clinical events

Period	Probable events	Clinical significance
Day 2-5 from infection	Gradual prodromes, sore throat, subfebrile temperature	Early window for recognition and isolation
Day 2-3 of illness	Formation of films, increase in local pain	Marker of toxemia in extensive films
Any week	Airway obstruction in laryngeal form	Risk of asphyxia, immediate assistance required
Weeks 1-2 and later	Myocarditis, heart rhythm disturbances	The main cause of mortality
Weeks 3-6 and later	Neuritis, paralysis of the soft palate, diaphragm, limbs	Risk of aspiration, respiratory failure

Forms of the disease and key symptoms

Form	Dominant traits	What's alarming
Oropharyngeal	Sore throat, thick gray-white films, low fever	Extensive films, "bull neck", tachycardia
Laryngeal	Hoarseness, barking cough, stridor	Rapid worsening of respiratory failure
Nasal	Mucopurulent, then bloody discharge, local film	Duration of symptoms, contact with the outbreak
Skin	Ulcers with a film or crust, clear edges	Slow healing, multiple lesions
Rare localizations	Conjunctiva, external auditory canal, genitals	Diagnostic errors without cultures and toxin testing

Assessing severity: clinical indicators

The severity of the disease is reflected by three groups of symptoms: the prevalence of the films, the severity of cervical edema, and systemic manifestations of toxemia. The larger the area of the films and the faster they spread, the higher the likelihood of early damage to the heart and nervous system. [13]

Cervical edema with a "bull neck" appearance, tender lymphadenopathy, increasing hoarseness, and stridor indicate a high risk of obstruction. This situation requires preparedness for early airway management by an experienced team. [14]

Systemic markers of severity include tachycardia, signs of heart failure, electrocardiogram conduction abnormalities, severe weakness, and confusion. Delay in seeking care, lack of vaccination, and the development of acute renal failure are associated with a worse prognosis. [15]

In children, respiratory complications are more common, sometimes with relatively mild local manifestations. This requires a lower threshold for hospitalization and observation. [16]

Table 2. Clinical and prognostic indicators of severe course

Indicator	What does it mean?	Action
Extensive films, rapid spread	High toxemia	Urgent inpatient assessment
"Bull neck", increasing stridor	Risk of obstruction	Preparedness for early intubation
Tachycardia, rhythm disturbances	Possible myocarditis	Monitoring, consultation with a cardiologist
Weakness of the soft palate, choking	Early neuritis	Aspiration prevention, speech therapy
Low vaccination rate, late treatment	High risk of complications	Aggressive surveillance tactics

Complications: heart

Myocarditis is the most common and dangerous complication. It can occur in the first week or later and presents with arrhythmias, conduction blocks, and signs of acute heart failure. Early development of myocarditis is associated with high mortality, necessitating rhythm monitoring even with moderate local symptoms. [17]

Critical forms include cardiogenic shock and severe arrhythmias requiring intensive care. Acute renal failure worsens the prognosis and is often associated with severe myocarditis. [18]

Even after stabilization, the risk of late cardiac complications should be considered. Patients should be monitored with symptoms, electrocardiograms, and echocardiography as indicated. [19]

Complications: nervous system

Neuritis most often affects the motor nerves. Typical early signs include nasalization of speech and choking due to soft palate paresis by the third week. Later, diplopia due to oculomotor nerve paresis, limb weakness, and rare cases of diaphragmatic paralysis with respiratory failure may develop. Most neurological disorders are reversible within weeks to months. [20]

Late neuritis requires multidisciplinary management involving a neurologist, rehabilitation specialist, and speech therapist. Prevention of aspiration is important, especially when associated with myocarditis and general weakness. [21]

Complications: respiratory tract and other organs

Airway obstruction develops due to membranes and edema, most often in the laryngeal form, and can develop rapidly. Key danger signs include increasing stridor, intercostal retractions, respiratory muscle fatigue, and decreased oxygen saturation. Immediate assessment with readiness to ensure airway patency is necessary. [22]

Secondary upper respiratory tract and ear infections are possible, as well as pneumonia, especially with swallowing disorders. Toxic renal damage has been reported, with the risk of acute failure in severe cases. These conditions require targeted monitoring and correction of fluid and electrolyte balance. [23]

Special groups and atypical presentations

Young children are more likely to develop respiratory complications more quickly. Even with a mild fever and sore throat, the combination of hoarseness, a barking cough, and stridor should be considered a reason to seek immediate medical attention. [24]

In partially vaccinated and fully vaccinated adults, milder and more atypical manifestations without a bright membrane are possible, increasing the risk of late diagnosis. Health authorities emphasize the need for clinicians to be vigilant, especially in cases of epidemiological links and travel. [25]

The cutaneous form can serve as a source of further transmission and is often associated with other cutaneous bacilli. Systemic effects of the toxin are less common, but the toxigenicity of the strain must be tested in the laboratory. [26]

Diagnostic Pitfalls and How to Avoid Them

The classic membrane is not always present, especially in vaccinated individuals, and mild respiratory cases may be indistinguishable from streptococcal pharyngitis. Therefore, if there are epidemiological grounds, swabs should be taken from the throat and nose, and in the cutaneous form, from the edge of the ulcer, followed by toxicity testing using reference methods. [27]

Strict red flag criteria are important for the clinic: increasing stridor, extensive membranes, "bull neck," tachycardia, and signs of heart failure, as well as any neurological symptoms. These signs require immediate hospitalization. [28]

Table 3. Red flags requiring immediate attention

Sign	Why is it dangerous?	Act One
Stridor and intercostal retractions	Risk of asphyxia	Urgent airway assessment
Extensive or rapidly growing films	High toxemia	Immediate referral to hospital
"Bull neck", painful neck	Increasing inflammation and swelling	Observation in the emergency department
Tachycardia, arrhythmias	Possible myocarditis	Rhythm monitoring, cardiologist consultation
Dysarthria, nasalization, choking	Early neuritis	Aspiration prevention, positional therapy

Who to distinguish during the initial examination

State	What is similar	What to rely on to differentiate
Streptococcal tonsillopharyngitis	Sore throat, plaque	No dense fused film, higher fever, rapid response to antibacterial therapy without antitoxin
Infectious mononucleosis	Plaques on tonsils, lymphadenopathy	Hepatosplenomegaly, severe fatigue, positive monotests
Candidiasis of the oropharynx	White plaques	Easily removed without bleeding, often immunodeficiency
Unprotected epiglottitis	Pain and dysphagia	High fever, toxic appearance, severe pain on laryngoscopy, urgent visualization
Pseudomembranous pharyngitis of other etiologies	Dense raids	Absence of toxigenic corynebacterium according to laboratory tests

Risk analysis by population

Population	The main risk	What to do
Children under 5 years old	Rapid respiratory failure	Low threshold for hospitalization and monitoring
Adults over 40 years of age	Higher mortality rate	Early escalation of observation, rhythm control
Unvaccinated and partially vaccinated	Severe course and toxemia	Aggressive diagnostic and monitoring tactics
Patients with late presentation	Late cardiac and neurocomplications	Long-term observation for up to several months
Cutaneous forms with multiple foci	Transmission and mixed flora	Laboratory verification of toxicity and sanitation of foci

What to do if you suspect diphtheria, taking into account complications

If there is any suspicion of respiratory disease, the patient should be isolated and referred to a hospital, with swabs taken and a clinical risk assessment conducted. Laboratory confirmation should not be awaited if there are signs of severe progression or red flags. Early action reduces the likelihood of irreversible toxic damage. [29]

Even after clinical improvement, monitoring for late complications is essential. Cardiac and neurological sequelae may manifest weeks later, so patient education and a schedule of follow-up visits are essential. Several guidelines emphasize the need for monitoring for up to three months after discharge in patients with severe complications. [30]

Health authorities remind us that a previous infection does not guarantee sufficient immunity. Patients with incomplete vaccination require catch-up immunization during their recovery period, and all close contacts should have their vaccination status assessed and be observed for up to ten days. These measures reduce the risk of new cases and delayed complications. [31]