Diphtheria is re-emerging in Europe, with the most recent cases presenting as skin infections in vulnerable groups.

The trend highlights the need to strengthen immunisation and improve clinician awareness of the clinical presentation and management of this disease.

Clinical Overview

Diphtheria is an acute bacterial infection that is most often caused by Corynebacterium diphtheriae. Its severity stems from the toxins produced by toxigenic strains, which can affect the heart, kidney, and nervous system.

The classic form is respiratory diphtheria, a febrile pharyngitis with pseudomembrane formation that can lead to airway obstruction and systemic toxin effects on the heart and nervous system.

Cutaneous diphtheria is characterised by pseudomembranes on preexisting wounds or ulcers. Corynebacterium ulcerans may produce clinical manifestations similar to those of C diphtheriae, whereas Corynebacterium pseudotuberculosis most often causes lymphadenitis.

Diphtheria is highly contagious and is transmitted mainly through respiratory secretions or contact with skin lesions and less commonly via contaminated objects.

Infections caused by C ulcerans are generally linked to contact with domestic animals (dogs or cats) and have not shown clear evidence of human-to-human transmission.

Cases of C pseudotuberculosis usually follow contact with small ruminants, particularly goats and sheep.

The incubation period is 2-5 days, and respiratory diphtheria has a fatality rate of 5%-10%.

Diagnosis relies on clinical assessment, culture of pharyngeal or cutaneous samples, and toxin testing confirmed by the National Reference Center for Corynebacteria of the Diphtheriae Complex at the Institut Pasteur in Paris, France, which serves as the national reference laboratory for diphtheria confirmation.

Vaccination Gaps

Since the introduction of mandatory diphtheria vaccination worldwide in the 1950s, its incidence has fallen sharply, making this infection rare.

In France, vaccination is included in the national schedule: primary vaccination from 2 months of age, a booster at 11 months, followed by recommended boosters at 6 years, 11-13 years, 25 years (adulthood), and 65 years, and then every 10 years thereafter. Diphtheria is a common notifiable disease. Vaccination is mandatory for healthcare workers and is recommended for travellers to endemic regions.

Adult vaccination rates remain low at approximately 50% among those aged 65 years or older, well below the 80%-85% needed for herd immunity.

Strengthening booster coverage, particularly among exposed and vulnerable groups, remains a priority in public health.

Vulnerable Groups

In 2022, Europe experienced its largest diphtheria outbreak in the past 70 years. Early cases were identified among migrants, followed by vulnerable populations, such as homeless individuals, individuals who inject drugs, unvaccinated individuals, and older adults.

Across Europe, 320 cases of diphtheria were reported in 2022, 165 cases of diphtheria in 2023, and 56 cases of diphtheria in 2024.

According to the European Centre for Disease Prevention and Control, France confirmed 52 diphtheria cases in 2022 and 18 in 2023, with the most recent infections reported as the cutaneous form.

Although the risk to the general population remains low due to high primary vaccination rates, adult vaccination rates are declining. Health authorities urge clinicians to ensure that the diphtheria vaccination status of the patients is up to date, particularly among socially or medically vulnerable populations.

Cutaneous Forms

A French multicentre retrospective study (2018-2022) found that resurgence of diphtheria coincided with a predominance of cutaneous compared with respiratory forms, a trend confirmed across Europe in 2022 (77% of which were cutaneous).

These forms are typically pustular, ulcerative, or necrotic; appear on preexisting wounds; and are frequently complicated by secondary infections with Staphylococcus aureus or Streptococcus species.

The study identified several diagnostic and surveillance challenges:

• Confusion with other bacterial skin infections, such as impetigo, can delay the appropriate diagnosis and treatment.
• Positive skin cultures for the C diphtheriae species complex are sometimes misclassified as contaminants, leading to missed or delayed diagnoses.
• Screening for or eradication of nasopharyngeal colonisation is rarely conducted outside outbreak investigations or contact tracing.
• Case traceability is limited, particularly among patients lost to follow-up or those in vulnerable populations such as migrants and homeless individuals.

This diagnostic underestimation likely reflects limited awareness of the cutaneous form of diphtheria among healthcare professionals, highlighting the need to improve the recognition of its varied presentations and appropriate management.

Clinicians should consider diphtheria in cases of persistent or worsening skin lesions, especially among individuals who have recently travelled to endemic regions or those living in vulnerable conditions.

Management and Control Measures

Diphtheria detection and management follow rigorous national guidelines. The main clinical and public health actions are as follows:

• Pharyngeal and/or skin swabs should be collected for culture and polymerase chain reaction testing of the tox gene, with prompt referral of toxin-positive isolates to a national reference laboratory for confirmation of the results.
• Patients should remain in isolation under contact and droplet precautions until two consecutive negative samples are obtained at least 24 hours apart or more than 24 hours after treatment has ended.
• Clinicians should assess for signs of severe disease, including laryngeal or respiratory obstruction; cardiac involvement, such as atrioventricular block or arrhythmia; and neurologic complications, such as descending paralysis.
• Antibiotic therapy with amoxicillin is recommended as the first-line treatment, with macrolides used in cases of penicillin allergy. Treatment should begin without delay, and equine diphtheria antitoxin should be promptly administered in confirmed or strongly suspected cases.
• Contact tracing should include all individuals exposed within the previous 7 days, with clinical monitoring, microbiological testing, antibiotic prophylaxis, and verification or updating of the vaccination status.

This story was translated from Univadis France.