Cellulitis Caused by Mixed Infection with Group A Streptococci and Non-Toxigenic tox-Gene-Bearing Corynebacterium diphtheriae: A Case Report

Abstract

Introduction

Cutaneous diphtheria has re-emerged in Europe, often presenting as skin-limited disease. Uncertainty around diagnosis, infection control, and toxigenicity testing can delay appropriate management.

Case Presentation

A 62-year-old woman experiencing homelessness presented with a 2-week history of a painful lower-leg eruption. This evolved from vesicles to bullae and shallow ulcers with a characteristic green-grey pseudomembrane, unresponsive to oral flucloxacillin. Swabs of the ulcer grew Corynebacterium diphtheriae and concurrent group A β-haemolytic streptococci, while throat swabs were negative. The national reference laboratory confirmed a non-toxigenic, tox-gene-bearing strain by tox polymerase chain reaction with a negative Elek test. After failing to respond to intravenous flucloxacillin, the patient was treated empirically with intravenous ceftriaxone, followed by oral azithromycin 500 mg once daily for 10 days, which led to complete clinical resolution.

Conclusion

This case highlights that skin-limited C. diphtheriae can mimic common skin infections and coexist with other pathogens. Key management priorities include (1) early lesion culture with specific request for C. diphtheriae and tox-gene testing; (2) prompt notification to public health authorities; and (3) implementation of appropriate infection-control precautions. For non-toxigenic cutaneous disease, a macrolide or penicillin-based antibiotic course is typically sufficient, and diphtheria antitoxin is generally not required.

Introduction

Cutaneous diphtheria is uncommon in high-income countries but persists and has re-emerged in Europe since 2022, with many cases presenting as skin-limited disease rather than classic pharyngeal diphtheria (often in settings of crowding, interrupted vaccination, or recent migration) [1, 2]. Typical lesions are slow-healing ulcers with a grey-green membrane, easily misclassified as impetigo, ecthyma, or mixed bacterial cellulitis [3]. Diagnosis is confirmed microbiologically from lesion samples, with specific request for Corynebacterium diphtheriae identification and toxigenicity testing (tox PCR ± Elek), because these results guide public-health management and distinguish toxigenic from non-toxigenic infection [3, 4]. Current guidance supports contact-based precautions for cutaneous lesions, while possible or admitted cases may require droplet and/or contact precautions depending on respiratory involvement and healthcare setting. We report a culture-confirmed non-toxigenic tox-gene-bearing (NTTB) cutaneous infection managed in dermatology, highlighting practical triggers to test, correct isolation, and coordination with public health, with brief context from recent European surveillance and guidance.

Case Presentation

A 62-year-old woman experiencing homelessness presented with a 2-week history of right-leg swelling and erythema. The area had become increasingly painful and warm, with clusters of vesicles around the ankle and foot that evolved into bullae and shallow ulcers covered by a green-grey pseudomembrane (Fig. 1). She was afebrile with stable observations and reported no throat symptoms, dyspnoea, or systemic toxicity. Before admission she had completed 7 days of oral flucloxacillin for presumed cellulitis without improvement.

Fig. 1.

a Dense bullous lesion with surrounding erythema on the medial aspect of the right leg. b Ulceration with a thick, greenish-grey pseudomembrane on the lateral foot, characteristic of cutaneous Corynebacterium diphtheriae infection.

At admission, lesion swabs were obtained before antibiotics were changed for microbiology and toxigenicity testing, and screening throat swabs were taken. Ulcer cultures grew C. diphtheriae with concurrent group A β-haemolytic streptococci, while throat swabs were negative. The national reference laboratory confirmed an NTTB strain by tox PCR with a negative Elek test, and public health was notified. UKHSA reference testing typically provides interim tox PCR results within 24 h of isolate receipt, with final reporting within 5 days [5]. Vaccination status was unknown. Isolation initially instituted as respiratory was, on advice, refined to contact precautions with covered lesions.

Initial empiric treatment in hospital consisted of intravenous (IV) flucloxacillin (2 g four times daily) for 2 days, which yielded no clinical response. Once culture results revealed a polymicrobial infection with C. diphtheriae and group A streptococci (GAS), and while awaiting formal toxigenicity and susceptibility results, therapy was broadened. Treatment was changed to intravenous ceftriaxone for 8 days to provide robust coverage for GAS cellulitis. Following this, oral azithromycin 500 mg once daily was administered for 10 days to specifically target C. diphtheriae, leading to significant clinical improvement. At discharge, the ulcers were granulating with reduced pain and exudate. No cardiac or neurological complications were observed. Clearance swabs taken at discharge were negative for C. diphtheriae. An outpatient review was arranged to monitor wound healing and to discuss updating her diphtheria-tetanus vaccination.

Discussion

Europe has seen sustained diphtheria activity since 2022 with a predominance of cutaneous presentations in vulnerable settings (crowding, interrupted vaccination, and reception centres) [1]. Contemporary cohorts and multi-country analyses confirm ongoing transmission and many skin-limited cases. These data justify a low threshold to test atypical ulcers in the right context [6, 7].

Diagnosis

Cutaneous lesions are clinically non-specific and often resemble ecthyma or cellulitis; co-pathogens are frequent on culture. In our case, the clinical presentation was best described as cellulitis with bullous change and pseudomembranous ulceration. In a German reception-centre cohort of toxigenic C. diphtheriae skin infections, 96% of erosive/ulcerative lesions were polymicrobial (GAS and Staphylococcus aureus common) [7]. Therefore, lesion swab culture with tox-gene PCR (±Elek) is decisive because it guides public-health management and distinguishes toxigenic from non-toxigenic infection [8, 9]. We distilled pragmatic recognition prompts to trigger testing/notification (Table 1); these are prompts, not diagnostic criteria, and confirmation requires microbiology plus tox testing.

Table 1.

Cutaneous Corynebacterium diphtheriae infection: recognition prompts and action checklist

Item	Details
Pattern	Slow-healing ulcer(s) with a grey-green pseudomembrane or adherent necrotic crust; may start as vesicles/bullae
Context	Crowded housing/reception centres, housing insecurity, unknown/interrupted vaccination, or recent travel to higher-incidence regions
Triggers to test	Poor response to anti-staphylococcal therapy or culture growing common co-pathogens (GAS, S. aureus)
How to sample	Swab beneath the pseudomembrane (or submit a small piece/exudate). Request targeted culture for C. diphtheriae with tox-gene PCR (±Elek)
Immediate actions	Start contact precautions with covered lesions and notify public health while results are pending
Treatment principles	Definitive antibiotics = macrolide or penicillin-class; antitoxin is not routine for skin-limited/NTTB infection; consider only for probable/confirmed toxigenic disease with respiratory symptoms or large cutaneous lesions after public-health consultation
Follow-up	Obtain clearance swabs per policy, review/update diphtheria-tetanus immunisation, and arrange a wound-care/safety-net plan

NTTB

NTTB strains are increasingly recognised in European cutaneous cases. They carry the tox gene but are phenotypically non-toxigenic (PCR tox-positive, Elek-negative). These strains can be transmitted between people, including within households [10, 11], yet current England guidance does not recommend routine contact tracing or post-exposure prophylaxis for NTTB cases; management focuses on clinical treatment, with public-health involvement mainly for surveillance and cluster support [12]. In our case, reference-laboratory testing identified a tox gene with a negative Elek result (NTTB), which is consistent with the absence of systemic toxicity despite extensive skin disease.

Management

Antimicrobial Therapy

First-line definitive treatment of C. diphtheriae is a macrolide or penicillin-class agent; antibiotics alone are usually sufficient for skin-limited disease [13]. In this patient, definitive therapy was oral azithromycin 500 mg once daily for 10 days, with clinical resolution and negative discharge cultures. In this NTTB case, diphtheria antitoxin was not indicated. Under current UKHSA guidance, NTTB strains are managed as non-toxigenic strains, whereas probable or confirmed diphtheria with respiratory symptoms and/or large cutaneous lesions (>2 cm²) should be assessed for DAT [14].

Local Wound Care

Standard moist wound care with lesions kept covered; change dressings under contact precautions. Cleanse with soap/water or normal saline; topical antiseptics optional per local protocol. For diagnostics, swab beneath the pseudomembrane (or submit a small piece); avoid aggressive debridement; keep it conservative only if clinically indicated; treat co-pathogens in parallel without altering diphtheria-directed therapy [12].

Infection Control

Infection-control measures should be matched to clinical presentation and setting. UKHSA guidance supports droplet and/or contact precautions for possible or admitted cases in healthcare settings, while contact-based precautions with covered lesions are appropriate for skin-limited presentations once respiratory involvement has been excluded. In our case, isolation was narrowed from initial respiratory precautions to contact precautions after respiratory disease was not identified [12].

Follow-Up

After treatment, arrange an early review to document clinical resolution; obtain clearance swabs per local policy and keep contact precautions until negative. Record/update diphtheria-tetanus immunisation, follow local public-health advice and complete any indicated public-health actions. Set a wound-care/safety-net plan to prevent loss to follow-up.

Pitfalls

• 1.Not swabbing before antibiotics: morphology is non-specific; confirm with culture + tox-gene PCR (±Elek) to determine toxigenicity.
• 2.Assuming polymicrobial culture excludes C. diphtheriae: co-pathogens are common (e.g., GAS, S. aureus); still act on a diphtheria isolate.
• 3.Over-simplifying isolation: precautions should reflect respiratory involvement and care setting; once respiratory disease is excluded, skin-limited cases may be managed with contact precautions.
• 4.Reflex DAT use: antitoxin is not routine for cutaneous/NTTB disease; consider only for probable/confirmed toxigenic infection with respiratory symptoms or large cutaneous lesions after public-health consultation.
• 5.Skipping the public-health/immune check: arrange clearance swabs, contact management, and diphtheria-tetanus vaccination review.

Anticipating these pitfalls shortens time to diagnosis, avoids inappropriate isolation, and ensures timely public-health engagement.

Social determinants: closing the loop. Recent European reports show that current diphtheria activity disproportionately affects people living in crowded settings or with disrupted access to vaccination and care, including residents of reception centres and those with housing insecurity. These contextual factors, not nationality, drive risk [7, 15]. The practical takeaway is unchanged: keep a low threshold to swab atypical ulcers, notify public health, use contact precautions for cutaneous disease, review/update immunisation, and arrange follow-up with clearance. This case report was prepared in accordance with the CARE guidelines, and the completed CARE checklist is provided as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000552211).

Statement of Ethics

Ethical approval was not required for this case report in accordance with local/national guidelines; the activity fell under clinical care and service evaluation. The patient provided written informed consent for publication of de-identified clinical details and images.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

No funding was received for this study.

Author Contributions

Conceptualisation, writing – original draft, visualisation (figure/table), and supervision/guarantor: M. Shanshal. Investigation/Clinical management, data curation (clinical details, images), and writing – review and editing: M. Shanshal and P.S. Wadhe. Both authors meet ICMJE authorship criteria.

Funding Statement

No funding was received for this study.

Data Availability Statement

All data underlying this case report are included in the manuscript and figures.