From Erysipelas to Epiglottitis: Managing Complications in Invasive Group A Streptococcal Infection

Introduction

Group A Streptococcus (GAS, Streptococcus pyogenes) is a gram-positive human-exclusive pathogen responsible for various types of infections, including pharyngitis and skin and soft-tissue infections. While pharyngitis is the most common manifestation of airway infections, lower airway infections such as epiglottitis and pneumonia can also be caused by GAS. Additionally, erysipelas and cellulitis are recognized as common manifestations. The incidence of invasive GAS infections, which can be severe and are associated with Streptococcal toxic shock syndrome (STSS), is increasingly reported worldwide [1]. In Norway, 243 cases were reported (4.5 cases per 100 000 population) during March 2022 to February 2023, followed by a large increase to 553 cases (10 cases per 100 000 population) between March 2023 and February 2024, while 230 cases on average were reported annually before. However, a case of erysipelas complicated by epiglottitis has not been previously reported. We present a case of a 76-year-old woman with invasive GAS infections. While she was initially diagnosed with erysipelas, she subsequently required intubation due to epiglottitis.

Case Report

A 75-year-old woman with a past medical history of cervical cancer, which was surgically treated 10 years ago, and dyslipidemia, presented to the Emergency Department (ED) with fever, swollen eyelids, and difficulty moving her body. Two days before presentation to the ED, she had a 38°C fever, which spontaneously disappeared the next day. At that time, she did not have any concerns about swelling. On the morning of the incident, her family found her collapsed in the living room, experiencing difficulty moving. Otherwise, her history was unremarkable.

On examination, the patient was alert, oriented, and able to follow commands. The following vital signs were obtained: blood pressure 140/88 mmHg, pulse 98 beats/min, respiratory rate 16 breaths/min, temperature 38.3°C, and oxygen saturation 96%. Her face was notable for well-circumscribed erythema and swelling of bilateral eyelids. She had tenderness and difficulty opening her eyes. Purulent discharge was coming from her inner canthus. She had no pain in other areas. Her lungs and heart were clear to auscultation and her abdomen was flat and soft.

Laboratory data (Table 1) revealed neutrophilia and thrombocytopenia (WBC 8500/µL (neutrophils 90.1%), Plt14.3×104/µL). CRP and procalcitonin levels were elevated at 100.9 mg/L and 5.62 ng/mL, respectively. The coagulation panel showed no remarkable changes. Bilateral edema of subcutaneous tissue was seen on non-contrast CT (Figure 1). Sputum culture and blood culture were positive for Streptococcus pyogenes.

The patient was admitted for antibiotic therapy. Because invasive GAS and STSS were confirmed (Table 2), cefazolin (1g q8h) was changed to ampicillin (2g q6h) + clindamycin (600mg q8h) [2,3]. Despite these antibiotics, edema spread to the forehead and malar region. Additionally, non-continuous swelling appeared on her neck on Day 3 in the morning. At the same time, she reported difficulty breathing without stridor. Contrast-enhanced CT (Figure 2) showed facial and pharyngeal edema. Based on her history, an anaphylactic reaction was unlikely. She had no history of trauma, burns, or repeated edema. Additionally, she had not been prescribed any medications that could cause toxicity or angioedema, such as iodine, angiotensin-converting enzyme inhibitors, or non-steroidal anti-inflammatory drugs. Her laboratory data showed normal liver, kidney, and thyroid function. The echocardiogram was within normal limits, and CT scans revealed no tumors. We suspected an invasive GAS-related lesion. Her symptoms deteriorated, and stridor appeared at noon. She was urgently intubated with a bronchoscope (Figure 3). A swollen and reddish epiglottis was observed and epiglottitis was diagnosed. A non-contrast-enhanced CT on Day 8 (Figure 4) indicated improvement in her larynx condition. On Day 11, her airway symptoms and swollen neck disappeared, and she was extubated. On Day 18, her antibiotic treatment was completed.

Discussion

Our patient was a 75-year-old woman with GAS infections whose first manifestation was typical erysipelas but which required intubation due to complicated epiglottitis.

Laryngeal edema can be caused by inflammatory and non-inflammatory diseases. Inflammatory edema results from infections, ulcers, trauma, and burns. Non-inflammatory edema can be triggered by hypersensitivity reactions, venous stasis (due to compression from mediastinal, cervical, and thyroid tumors), aortic aneurysms, angioedema [4], iodism [5], myxedema, and generalized edema associated with conditions like heart failure and liver and kidney dysfunction [6]. In this case, CT showed pharyngeal edema with swollen epiglottis. Sputum and blood culture were positive for S. pyogenes, and invasive GAS was previously confirmed. We clinically diagnosed epiglottitis associated with invasive GAS infections, but could not collect culture specimens of the epiglottis due to her rapid respiratory deterioration and difficulty in intubation. In addition to this, the possibility remains that the sputum culture results were contamination because pneumonia was not observed.

Therefore, we had limitations in our diagnosis, but concomitant surface and blood GABS cultures are more likely to be positive in fulminant cases or in the presence of immune compromise [7]. We thought the concordance between the sputum culture and blood culture results was important information.

Underlying illnesses and medical conditions increase the risk for GAS infection such as skin condition (eg, burns, wounds, and chronic skin breakdown), chronic illness (eg, cirrhosis, obesity, diabetes, and chronic obstructive pulmonary disease), and immunosuppression (eg, sickle cell disease, nephrotic syndrome, human immunodeficiency virus [HIV]/AIDS, and cancer). M protein type is also thought to be one of the risk factors of invasive GAS infection [8]. The M protein is a dimeric coiled-coil fibrillar protein that extends from the bacterial cell wall, and GAS is classified based on the sequence of the 5’ end of the gene encoding the M protein (emm) [9]. Other virulence factors, including streptokinase, SpeB, and superantigens (SpeA, SpeC, and SSA), can worsen invasive GAS. The emm type of GAS can vary from site to site [10] and some virulence factors are common in different GAS diseases. These superantigens have been linked with increased fitness and virulence of contemporary GAS strains causing scarlet fever and invasive disease. Also, the mechanisms of mucosal-associated invariant T cells were recently shown to be highly activated in patients with STSS as host response, and these cells can contribute GAS pharyngitis [9]. These findings indicate that microbiological virulence factors and host responses can explain secondary epiglottitis in this case. However, we could not analyze these factors due to our technological issues. This is another limitation.

In pediatrics, epiglottitis caused by GAS has long been reported [11–13]. Since the introduction of H. influenzae type B vaccine, the incidence of H. influenzae type B epiglottitis has declined. This has led to a relative increase in epiglottitis due to GAS, while the increase in GAS infections has also caused an increase in epiglottitis due to GAS [14,15]. Although there have been a few reports of epiglottitis caused by GAS in adults [16], there are no previous cases of invasive GAS infections resulting in intubation due to secondary epiglottitis, as observed in the present case.

Initially, our patient was diagnosed with erysipelas based on her typical facial manifestation. However, her deterioration indicated not only localized skin infection but also systemic inflammation. In erysipelas, 4.6% of 607 patients had positive blood cultures, of which 46% were Streptococcus pyo-genes, 29% were other b-hemolytic streptococci, 14% were Staphylococcus aureus, and 11% were gram-negative organisms [17]. Bacteremia is thought to be more common in GAS than in other causative organisms, but even so, it is not frequent, occurring in only about 2% of cases. Among invasive GAS infections, skin and soft-tissue infections are common, but bacteremia and sepsis are also common in patients over 65 years of age. Epiglottitis and otitis media have been reported to occur in 1% of patients over age 65 [8]. Therefore, when invasive GAS is suspected, it is crucial to monitor the patient’s progress carefully for complications, including epiglottitis.

Conclusions

The case report describes a 75-year-old woman with invasive GAS infections whose initial manifestation was typical erysipelas, but she required intubation due to complicated epiglottitis.

GAS epiglottitis is less common in adults than in pediatric patients, and there are no previously published cases of invasive GAS infections resulting in intubation due to secondary epiglottitis, as observed in the present case. Even when GAS disease is suspected and treated with antibiotics, it may be difficult to prevent subsequent invasive GAS disease [18]. Regardless of the diagnosis upon admission and initial treatment, it is necessary to observe patients carefully, and once invasive GAS infection is suspected, preparation for urgent intervention is required.