Bilateral periorbital necrotising fasciitis associated with invasive group: a Streptococcus infection

Abstract

A previously independent 56-year-old immunocompetent woman presented with septic shock in the setting of periorbital swelling and diffuse infiltrates on chest imaging. Blood cultures were positive for growth of group A Streptococcus (GAS). Broad spectrum antimicrobials were initiated with the inclusion of the antitoxin agent clindamycin. Necrosis of periorbital tissue was noted and surgical consultation was obtained. Débridement of both eyelids with skin grafting was performed. GAS was isolated from wound cultures and also observed on periorbital tissue microscopy. The final diagnosis was bilateral periorbital necrotising fasciitis (PONF) associated with invasive GAS infection. The patient had a prolonged intensive care unit course with input from multiple specialist teams. This case demonstrates the importance of early recognition and treatment of PONF, the profound systemic morbidity caused by these infections, and illustrates successful multidisciplinary teamwork.

Background

Periorbital necrotising fasciitis (PONF) is one of the more challenging diagnoses encountered by the ophthalmologist. The initial presentation may resemble a relatively benign pre-septal cellulitis. Meanwhile, the disease progresses rapidly below the dermis, often with devastating consequences. Necrotising fasciitis (NF) is more commonly seen in the abdominal wall, perineum and extremities; PONF is exceedingly rare. A retrospective British Ophthalmological Surveillance Study found 30 new cases of PONF over a 2-year period between 2010 and 2012, suggesting an incidence of 0.24 per million per annum.¹ Potential outcomes range from severe disfigurement, damage to the globe with loss of vision and even death.

We describe a case of bilateral PONF in the setting of invasive group A Streptococcus (GAS) infection, with profound associated morbidity in a previously independent, immunocompetent 56-year-old woman. This case highlights the potential for devastating complications in PONF. Early identification, introduction of broad-spectrum antibiotics and early surgical consultation with multidisciplinary team involvement is critical.

Case presentation

A 56-year-old woman was found obtunded in bed surrounded by vomitus, with Glasgow Coma Scale of 8 and significant bilateral periorbital swelling. She lived alone and her medical history was significant for hypertension, alcohol excess and obesity. On arrival to the local emergency department, she was found to be febrile, hypotensive and hypoxic. She had two episodes of pulseless electrical activity and return of spontaneous circulation was obtained following C reactive protein (CPR) on both occasions. She was intubated in the emergency department.

Initial laboratory investigations revealed C reactive protein (CRP) 523 mg/L, white cell count (WCC) of 18.5×10⁹/L, haemaglobin 108 g/L, sodium 139 mmol/L, glucose 14 mmol/L and creatine kinase >1000 U/L. The Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC) score was 10. CT brain demonstrated pronounced oedema in the preseptal tissue of both orbits, without evidence of postseptal involvement. Fat stranding present in the left side of the face was concerning for facial cellulitis (figure 1). CT chest showed progressive atelectatic changes within the lungs and small to moderate pleural effusions. Ventilatory support and continuous venous haemodialysis filtration were commenced due to hypoxia and acute kidney injury with associated metabolic acidosis. Blood and sputum cultures grew GAS. She was commenced on vancomycin, benzylpenicillin, meropenem and clindamycin. Four days following presentation, she was transferred to our tertiary centre for further input from ophthalmology and plastic surgery due to progression of periorbital infection.

Figure 1.

CT brain demonstrating pronounced oedema in the preseptal tissue of both orbits.

On initial examination, there was a well-demarcated severe bilateral periorbital exudative oedema with necrotic peripheries, and a smaller area of necrotic tissue at the left malar region (figure 2A, B). LRINEC score was now 8. Ophthalmic assessment showed intact globes with severe chemosis, clear corneas, formed anterior chambers and no evidence of intraocular infection in the anterior or posterior segments. The posterior lamellae appeared preserved. Débridement of bilateral upper and lower lids was performed in theatre the following day, with preservation of the posterior lamella (figure 3A). GAS was isolated from wound cultures and also observed on periorbital tissue microscopy. Histopathology reported little muscle, fat, skin and fibrous tissue set within necrotic debris, and dense acute inflammatory infiltrate. Full-thickness skin grafting from the thigh to both upper and lower lids was performed 5 days later (figure 3B). This site was chosen as large amounts of skin were required, precluding traditional graft harvesting sites such as the preauricular area, while vascular access had been placed in the upper arms. Meropenem, vancomycin and clindamycin were stopped on day 5. Tracheostomy was inserted to facilitate ventilatory weaning.

Figure 2.

(A, B): Bilateral periorbital exudative oedema with necrotic peripheries, and a smaller area of necrotic tissue at the left malar region.

Figure 3.

(A) Eyelids immediately post debridement. (B) Eyelids with bilateral upper and lower skin grafts taken from right thigh. (C) Follow-up picture of eyelids 6 weeks postoperatively.

Benzylpenicillin was discontinued and she was then treated with oral amoxicillin. On day 18 of admission, she was medically stable and transferred back to her local hospital following a prolonged stay in the intensive care unit. Visual acuity (VA) was preserved, and she continued to experience difficulty opening her eyes spontaneously.

Differential diagnosis

The initial differential in this case included sepsis in the setting of preseptal cellulitis, orbital cellulitis and anaphylaxis. The progression and necrotic changes were concerning for development of NF and prompted transfer to a tertiary centre for ophthalmological and surgical consultation. NF was high on the differential given the clinical picture, microbiology and elevated LRINEC score. Type II NF is characterised by isolation of GAS with or without other bacterial species, as seen in this case.

Outcome and follow-up

The patient spent a further 10 days at a rehabilitation unit following discharge from her local hospital. Her tracheostomy was successfully decannulated, with full recovery of renal function. At 6-week follow-up, her Snellen VA was 6/6 bilaterally. She had poor levator function, abnormal lid position and thick grafts but no lagophthalmos and could adequately open her eyelids to clear the visual axis (figure 3C). Longer term follow-up will await full graft healing and remodelling, and assess any deficiencies that could be addressed.

Discussion

The diagnosis in this case is invasive GAS infection with sequela of toxic shock syndrome (TSS). While GAS usually results in a mild pharyngitis or non-necrotising soft tissue infection, virulence factors can lead to invasion and TSS. M proteins suppress neutrophil phagocytosis, allowing for disease entry into the host, and exotoxins A and B may stimulate cytokine release causing shock, organ failure and immune suppression.² Based on the patient’s initial presentation, it is likely that periorbital cellulitis was a portal of entry for invasive GAS infection, with development of bacteraemia, pneumonia and septic shock. While unusual, progression of PONF over the course of days (‘stalled NF’) has been described.³ GAS is cultured in up to three quarters of cases of PONF^{1 4 5} co-infection with Streptococcus aureus has occasionally been reported.⁴

PONF is an uncommon but potentially devastating condition caused by rapidly spreading inflammation with progressive vascular thrombosis and subcutaneous necrosis, and is seen bilaterally in 35% of cases.⁶ The most common precipitating event for this condition is minor penetrating or surgical trauma, but in 26%–28% of all cases, no trigger is identified, consistent with this case and previous reports of ‘unprovoked NF’.^{4 6 7} Predisposing factors for the development of NF include systemic immunocompromising conditions such as diabetes mellitus, intravenous drug use, old age, in addition to alcoholism and obesity,⁶ both present in this case.

Although PONF has a better prognosis than NF at other sites, (mortality rate 8.5% compared with 22%),⁶ morbidity may be severe and includes blindness (14%), TSS (29%), soft tissue defect (44.6%) and orbital cellulitis.⁶ The reasons for this disparity in mortality are manifold. The thin eyelid skin lacks much subcutaneous fat, and infection is often noticed earlier in its course—the signs of necrosis are more obvious.⁴ In addition, the rich vascularisation of the eyelids allows for better antibiotic penetrance of the inflamed area. The eyelids exhibit a unique phenomenon of auto-demarcation in PONF which enables delayed and less extensive débridement.⁸

As in all cases of NF, time is tissue. The diagnosis should be made clinically without the need for supportive imaging. Pain out of proportion to skin manifestations of disease is the most consistent feature noted at time of presentation.⁹ The LRINEC score may be useful in differentiating advanced soft tissue infections from NF. A series of baseline laboratory studies including haemoglobin, CRP, WCC, creatinine, sodium and glucose are used to stratify risk of NF. While not particularly sensitive, a score >6 should raise suspicion for NF and prompt surgical consultation for potential debridement.¹⁰ The LRINEC criteria have limitations; one case series of 11 patients did not find a correlation between LRINEC score and severity of PONF.¹¹ Frequent re-evaluation of patients with apparent periorbital cellulitis with monitoring of pain parameters is essential.

Until a pathogen is identified, empirical treatment with carbapenem, methicillin-resistant S. aureus coverage and clindamycin should be initiated. Clindamycin is an important asset in the physician’s armamentarium. The mechanism of action of macrolides is the inhibition of the 50 S subunit of the bacterial ribosome. This not only inhibits bacterial reproduction but also the production of other bacterial proteins including the GAS M proteins and pyogenic exotoxins that play a key role in the pathophysiology of NF. Once cultures are obtained and GAS is confirmed, de-escalation to penicillin G in combination with clindamycin is appropriate. Intravenous immunoglobulin is often given in cases of streptococcal TSS; this approach is supported by a recent meta-analysis showing significant reduction in 30-day mortality.¹² Hyperbaric oxygen therapy has been reported in a small number of patients with streptococcal TSS. The efficacy of this treatment modality is unclear in the absence of controlled trials.¹³

Patient’s perspective.

My mum lives alone, and when I couldn’t get in contact with her I stopped by to check she was OK. I found her unresponsive with horrific eye infections. When the ambulance arrived the paramedics had to take precautions for COVID-19, but as soon as they saw her eyes they told us they had never seen anything like it. It was a little unnerving to hear that.

That night was the worst night of my life. Mum suffered two cardiac arrests soon after arriving at hospital. She was revived each time but we were warned about how severe her condition was. While they were concerned about her eyes, they didn’t get much of a mention as her organs had started to fail. The conversations we were having were all centred on ‘if’ she survives. My brothers and I went home that night so sure that we were going to lose our mum.

Having someone you love in the ICU is surreal, you know it’s them but you don’t recognise them with all the tubes, machines, leads and pumps keeping your loved one alive. Mum had all of that plus her eyes covered most of the time. At times the only part I could look at and think yep thats her was looking at her feet or hands with her painted nails. She also wouldn’t be able to see as she was still recovering from the grafts. I was terrified by the thought that she would wake up and not know what had happened, surrounded by people she didn’t know and not be able to see or communicate.

Once she got through the first few days, there was a glimmer of hope that she may survive, but we had also been warned that her quality of life may not be great. The focus had changed from just keeping her alive to managing her injuries so she could have a good long-term recovery. After 5 days she was moved to a bigger hospital, while she was there she had surgery to remove the dead tissue from her eyes so the infections could be controlled. Early on we were so terrified that her vision would be affected. She is such an independent, strong, confident woman, the thought of her needing constant assistance was quite scary.

The most difficult thing about mum being in hospital was constantly following for updates, I wouldn’t hear from the doctors unless they wanted consent for a procedure or a surgery. We live 95 km from the hospital and there were restrictions on visiting which made things difficult. They were preparing the ICU for COVID-19 and visitors had to stand or sit in the hallway and look through glass doors. It was exhausting travelling all that way to peer through glass doors. I would be hit with all of the emotions on the long drive home and just cry the whole way there.

Over the next few weeks she hit milestone after milestone. We had a rotating roster of who was visiting each day so that she never went a day without seeing someone she knows. She was moved to a ward, then moved back to a more local hospital then moved to rehab. After 6 weeks she was ready to come home. We slowly crossed off all the major issues she had to recover from. I had never had someone close to me be so sick, go through such a big recovery or be treated by such a multidisciplinary team of doctors and specialists. It was amazing to see the incredible things that can be done to treat and heal the body. We went from having a fairly healthy mum, to being as close to dead as you can get, to bringing her home. There is still a long time to go but I’m so thankful we have got this far. Not only is she alive but will be able to see and live an independent life.

Learning points.

• A high degree of clinical suspicion with frequent evaluations of self-reported patient pain scores can assist with early identification of periorbital necrotising fasciitis (PONF).

• The Laboratory Risk Indicator for Necrotising Fasciitis scoring system can be useful for risk stratification but has limited sensitivity.

• As soon as the diagnosis is suspected, broad-spectrum antimicrobials should be initiated, with inclusion of the antitoxin agent clindamycin.

• Ultimately source control with surgical débridement is the definitive treatment, and early surgical consultation should be obtained in all cases where PONF is suspected.