Diphtheria: Symptoms, Types, Causes and Treatment

Diphtheria is a serious infectious disease that, despite being largely preventable, continues to pose a threat in many parts of the world. Known for its dramatic symptoms and potentially fatal complications, diphtheria has re-emerged in recent years in some regions due to lapses in vaccination coverage. In this article, we’ll take a comprehensive look at diphtheria’s symptoms, types, causes, and treatment, synthesizing the latest research and clinical insights to help you understand this important public health concern.

Symptoms of Diphtheria

Diphtheria often begins innocuously, mimicking a common sore throat. But behind these mild beginnings can lurk a rapidly escalating infection with life-threatening potential. Recognizing the symptoms early is vital, as timely intervention can mean the difference between full recovery and severe complications.

Symptom	Description	Severity/Complications	Source(s)
Sore throat	Painful, inflamed throat	Common early sign	1 2 3 4
Fever	Mild to moderate temperature increase	Typical onset	1 2 3 4
Pseudomembrane	Gray/white membrane in throat/nose	Obstructs airway, hallmark	1 2 3 4 7
Bull neck	Swelling of neck tissues	Sign of severe disease	1 2 4
Difficulty swallowing	Trouble eating or drinking	Indicates progression	1 3
Respiratory distress	Breathing difficulties	Severe, can be fatal	3 4
Myocarditis	Heart inflammation	Life-threatening	1 4 11
Neuropathy	Nerve damage (paralysis)	Delayed complication	1 5 13

Table 1: Key Symptoms

Key Clinical Features

Diphtheria typically starts with an onset of sore throat and fever. The most distinctive feature is the formation of a thick, grayish-white pseudomembrane covering the tonsils, pharynx, or nasal cavity. This membrane is tightly adherent and can bleed if disturbed, often leading to airway obstruction if left untreated 1 2 3 4 7.

Patients, especially children, may develop a swollen neck—often called “bull neck”—due to enlarged lymph nodes and soft tissue swelling. Other frequent complaints include difficulty swallowing (dysphagia), pain during swallowing (odynophagia), and general malaise 1 2 3.

Complications and Severe Manifestations

Diphtheria can be deadly, primarily because of complications stemming from the diphtheria toxin. If the toxin spreads beyond the throat, it can cause:

• Airway blockage: The pseudomembrane may obstruct breathing, requiring emergency intervention 1 3 4.
• Myocarditis: Inflammation of the heart muscle, leading to arrhythmias and heart failure 1 4 11.
• Neuropathy: Cranial and peripheral nerve paralysis, which can manifest days to weeks after initial symptoms 1 5 13.
• Renal impairment: The toxin can damage the kidneys, sometimes resulting in acute renal failure 3.
• Hemorrhagic features: Bleeding from the gums or nose, and low platelet counts, have been linked to poor prognosis 3.

Disease Progression and Risk Factors

Most diphtheria deaths are the result of late recognition and lack of prompt treatment. The risk of severe disease is higher in unvaccinated individuals, but cases have occurred even among vaccinated children, emphasizing the importance of booster doses and early clinical suspicion 1 2 4 14. Complications such as myocarditis and respiratory distress are associated with higher mortality rates 1 3 4 11.

Types of Diphtheria

Not all cases of diphtheria look alike. The disease can present in various forms, depending on the site of infection and the causative bacterial strain. Understanding these types helps clinicians diagnose and manage cases more effectively.

Type	Affected Area	Typical Features	Source(s)
Respiratory	Throat, tonsils, nose	Pseudomembrane, sore throat, bull neck	2 3 4 7 11
Cutaneous	Skin wounds	Non-healing ulcers, membranes	10 11
Pharyngeal	Pharynx, tonsils	Throat pain, pseudomembrane	1 2 7
Laryngeal	Larynx (voice box)	Hoarseness, airway obstruction	7 11
Nasal	Nasal mucosa	Bloody, purulent nasal discharge	2 7 11
Zoonotic	Animals to humans	Similar to classical forms	8 9 10

Table 2: Types of Diphtheria

Respiratory Diphtheria

This is the classic and most dangerous form, typically affecting the throat (pharynx), tonsils, and sometimes extending to the larynx or nasal cavity. It is characterized by the formation of a thick pseudomembrane and the risk of airway compromise. “Bull neck” swelling is most commonly seen in this type 2 3 4 7 11.

Cutaneous Diphtheria

Cutaneous diphtheria presents as chronic, non-healing skin ulcers covered by a gray membrane. It is more common in tropical and resource-limited settings and can be caused by either C. diphtheriae or C. ulcerans 10 11. While less likely to cause systemic complications, cutaneous lesions can be a reservoir for transmission.

Other Anatomical Forms

• Pharyngeal and Tonsillar: The most common sites, with pain, pseudomembrane, and swelling 1 2 7.
• Laryngeal: Hoarseness, stridor, and potential airway obstruction due to membrane extension 7 11.
• Nasal: Bloody, purulent nasal discharge and mild systemic symptoms 2 7 11.

Zoonotic Diphtheria

In recent years, Corynebacterium ulcerans, often transmitted from domestic animals like cats and dogs, has emerged as a cause of both respiratory and cutaneous diphtheria, especially in developed countries 8 9 10. These zoonotic forms can be clinically indistinguishable from classical diphtheria and highlight the need for vigilance even in low-incidence settings.

Causes of Diphtheria

The root cause of diphtheria is a bacterial infection, but the real damage is inflicted by a potent toxin. Understanding what drives the disease—both in terms of the bacteria involved and how it spreads—is key to prevention and control.

Cause	Description	Relevance/Notes	Source(s)
Corynebacterium diphtheriae	Gram-positive bacterium; main agent	Produces toxin, causes most cases	1 6 7 11 14
C. ulcerans	Zoonotic Corynebacterium species	Increasingly common in Europe	8 9 10
C. pseudotuberculosis	Rare human pathogen	Occasional human cases	10 11
Diphtheria toxin	Exotoxin encoded by tox gene	Responsible for systemic effects	11 13 14
Human-to-human transmission	Respiratory droplets, direct contact	Main mode of spread	4 11 14
Animal-to-human transmission	Contact with infected animals	C. ulcerans, rare but rising	8 9 10

Table 3: Main Causes and Transmission

Bacterial Agents

• Corynebacterium diphtheriae is the primary culprit. Several biotypes exist, including Gravis, Intermedius, Mitis, and Belfanti, all of which can produce the disease-causing toxin 6 7 11.
• C. ulcerans and, rarely, C. pseudotuberculosis can also cause diphtheria in humans, especially in regions with close animal contact or poor sanitation 8 9 10 11.

The Diphtheria Toxin

The hallmark of the disease is the diphtheria toxin, an exotoxin encoded by the tox gene. This toxin inhibits protein synthesis in cells, leading to tissue death, organ dysfunction, and the classic signs and complications of diphtheria 11 13 14. Only toxigenic strains cause classic, severe diphtheria; non-toxigenic strains may cause milder disease or act as carriers.

Modes of Transmission

• Person-to-person: Diphtheria spreads mainly via respiratory droplets when an infected person coughs or sneezes. It can also spread by direct contact with skin lesions or contaminated objects 4 11 14.
• Zoonotic: C. ulcerans can be transmitted from animals, particularly domestic pets, to humans, accounting for sporadic cases in developed countries 8 9 10.

Factors Influencing Outbreaks

Low vaccination coverage, waning immunity among adults, and crowded living conditions are the primary drivers of ongoing outbreaks and re-emergence of diphtheria in both developing and developed regions 1 6 8 10 14.

Treatment of Diphtheria

Diphtheria is a medical emergency that requires prompt and coordinated care. The cornerstone of treatment is neutralizing the toxin and eradicating the bacteria. However, access to lifesaving antitoxin and appropriate antibiotics remains a challenge in many parts of the world.

Treatment	Purpose	Key Facts/Challenges	Source(s)
Diphtheria antitoxin (DAT)	Neutralizes circulating toxin	Most effective when given early; supply limited	1 4 11 13 14 15
Antibiotics	Kill bacteria, prevent transmission	Penicillin and erythromycin; resistance possible	12 14
Supportive care	Manage complications	Airway management, cardiac monitoring	1 3 4 11
Vaccination	Prevention, post-exposure prophylaxis	Reduces severity and transmission	1 6 10 14

Table 4: Main Treatments

Antitoxin Therapy

• Diphtheria antitoxin (DAT) is the only treatment that neutralizes the circulating toxin before it binds to tissues 1 4 11 13 14 15.
• Early administration is critical; once the toxin is bound, the antitoxin cannot reverse the damage.
• Traditionally derived from horse serum, DAT can cause allergic reactions and serum sickness. Human-derived or recombinant alternatives are being explored 13 15.
• Global shortages and access barriers make DAT difficult to obtain in many regions, posing serious risks during outbreaks 15.

Antibiotic Therapy

• Antibiotics are essential to eradicate C. diphtheriae, halt further toxin production, and prevent transmission.
• Penicillin is generally preferred, with erythromycin as an alternative 12 14. Both are effective; however, penicillin may clear fever more rapidly 12.
• Antibiotic resistance, particularly to erythromycin, has been reported in some settings 12.
• Antibiotics alone do not neutralize toxin already circulating in the body, which is why they must be combined with DAT for optimal outcomes 14.

Supportive and Preventive Care

• Airway management is often necessary for patients with severe pharyngeal or laryngeal involvement; intubation or tracheostomy may be required 1 3 4.
• Cardiac monitoring for signs of myocarditis is vital, as is neurological evaluation for early detection of neuropathy 1 3 4 11.
• Vaccination remains the cornerstone of prevention. Booster doses are essential, especially as immunity wanes with age 1 6 10 14.
• Isolation of infected individuals and prompt public health response are crucial to prevent further spread 14.

Challenges in Treatment

• Delayed diagnosis and treatment greatly increase the risk of fatal complications.
• Limited availability of antitoxin, especially in regions where diphtheria is rare, remains a significant challenge 15.
• Vaccine hesitancy and gaps in coverage can lead to outbreaks, even in countries with previously high immunization rates 1 8 10 14.

Conclusion

Diphtheria is a preventable but potentially devastating disease that continues to threaten global health, particularly where vaccination coverage is low. Its symptoms can be dramatic and life-threatening, but early recognition and treatment can save lives. Here’s what we’ve learned:

• Key symptoms include sore throat, fever, pseudomembrane formation, and “bull neck” swelling.
• Types of diphtheria vary by location (respiratory, cutaneous, nasal, laryngeal) and causative organism.
• Causes stem from infection with toxigenic Corynebacterium species, primarily C. diphtheriae, and spread via respiratory droplets or contact with infected animals.
• Treatment requires urgent administration of diphtheria antitoxin and antibiotics, alongside supportive care and public health measures.
• Vaccination remains the most effective preventive tool, but ongoing vigilance is needed to maintain high coverage and rapid outbreak response.

Staying informed about diphtheria’s evolving epidemiology and ensuring access to lifesaving interventions is essential to keep this ancient foe at bay.