Periorbital necrotising fasciitis with underlying undiagnosed hepatitis C infection

Abstract

We report the case of a 56-year-old man, previously well, who presented with a spontaneous right-sided periorbital necrotising soft tissue infection and subsequently found to have undiagnosed hepatitis C and liver cirrhosis. The patient presented with rapid onset right eye pain, periorbital swelling and septic shock. CT scan revealed diffuse inflammatory changes to the soft tissue anterior to the right eye. The initial treatment included intravenous antibiotics, emergency debridement of necrotic tissue and admission to intensive care. Group A streptococcus was cultured from the debrided tissue. The patient developed decompensated liver failure and life-threatening haematemesis. Liver screening detected hepatitis C positive serology, the only risk factor for which was an old tattoo. The patient was effectively managed by early involvement of multiple clinical teams. We review the literature surrounding periorbital necrotising fasciitis, discuss the evidence for hepatic disorders as a potential cause and make recommendations for managing these patients.

Background

Necrotising fasciitis (NF) is an uncommon but highly destructive soft tissue infection that can affect any part of the body; typically, the extremities, perineum and trunk. Few cases affecting the head and face have been described.

NF is characterised by rapidly progressive inflammation, underlying vascular thrombosis and eventual tissue necrosis, leading to severe sepsis and possible death. Mortality from NF is high and prognosis is related to the time until diagnosis and treatment.

NF usually occurs following a break in the dermis; lacerations, abrasions, burns, insect bites, puncture wounds or following surgery. This exposes the underlying tissue to infection. Moreover, predisposing factors impair immunological defences further. Susceptible patients are often immunocompromised by conditions such as diabetes mellitus, chronic kidney disease or malignancy. In this article, we review the literature relating to NF and its association with immunocompromising hepatic conditions, in particular hepatitis.

Case presentation

A 56-year-old man with no significant medical history presented to the emergency department with a sudden onset of right eye pain and a lower eyelid soft tissue swelling. Despite intravenous antibiotic treatment, the swelling progressed. The patient developed skin necrosis adjacent to the right medial canthus and systemic signs of sepsis: tachycardia, tachypnoea, elevated serum lactate and thrombocytopenia. The patient was transferred to a tertiary centre with plastic surgery expertise for emergency surgical debridement of suspected periorbital NF. On arrival, the patient had a heart rate of 112 bpm, blood pressure of 132/63 mm Hg, respiratory rate of 24 bpm, oxygen saturations of 98% on room air and a temperature of 36.9°C. On examination, he showed extensive erythema on the right side of the face and periorbital swelling with restricted opening of the right eye (figure 1). He had a 10×10 mm area of necrosis of the right medial lower eyelid. His visual acuity and extraocular movements were unaffected. On admission, blood tests revealed a white cell count of 8.0, C reactive protein (CRP) of 25 and serum lactate of 4.6. His Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC) score was 2. A preoperative CT scan (figure 2) showed diffuse inflammatory changes to the soft tissues anterior to the right eye with no swelling within the orbit itself.

Figure 1.

Preoperative clinical presentation.

Figure 2.

Preoperative CT scan.

His previous medical history was unremarkable. He denied any recent use of non-steroidal anti-inflammatory drugs (NSAIDs), a known risk factor for NF. His wife and three children at home were all well, with no history of streptococcal sore throat. He had no relevant family, alcohol or drug history, and no allergies.

Surgical debridement of the orbit was performed (figure 3) and intravenous antibiotics continued. Intraoperative wound swabs and tissue samples were sent for examination. Urgent Gram staining revealed Gram-positive cocci, confirmed to be a group A streptococcus on culture. Postoperatively, the patient was admitted to the intensive therapy unit (ITU) for inotropic support due to septic shock, acidosis and rising lactate (12.4). Here, the patient was noted to be present with jaundice and encephalopathy. Liver function tests were deranged and a non-invasive liver screening revealed positive hepatitis C serology. A second urgent debridement was performed the following day (figure 4), and the patient improved with intravenous antibiotics, immunoglobulins and inotropic support. The patient was stabilised and stepped down to the gastroenterology ward where he suffered an oesophageal variceal bleed, secondary to portal hypertension, which required emergency ligation banding and a further ITU admission. The patient was discharged following medical optimisation and attended for reconstruction of the lower eyelid ectropion with a full-thickness skin graft as a semielective procedure.

Figure 3.

First debridement postoperative image.

Figure 4.

Day 1 post surgery. Indication for second urgent debridement (tracking erythema marked).

Investigation

On admission, routine blood tests showed a white cell count of 8.0 × 10⁹/L, CRP of 25 and an LRINEC score of 2. Arterial blood gas analysis revealed a pH of 7.20 and serum lactate of 4.6.

A CT scan of the head and orbits (figure 2) confirmed diffuse inflammatory changes to the soft tissue anterior to the right eye with no swelling within the orbit itself.

Intraoperative tissue samples and wound swabs taken for urgent Gram staining revealed Gram-positive cocci with group A streptococcus confirmed on culture of the specimens and blood culture samples.

Deranged liver function tests were identified on ITU. Subsequent investigation identified positive hepatitis C antibodies, with liver cirrhosis, portal hypertension, abdominal varices and splenomegaly subsequently seen on abdominal ultrasound and CT scanning.

Differential diagnosis

Given the rapid deterioration of the patient and severe septic response to infection, the working diagnosis in this patient was a periorbital NF. Important differential diagnoses included periorbital cellulitis, orbital myositis, cavernous sinus thrombosis, chalazion and idiopathic orbital inflammation.

Treatment

The mainstay of treatment was urgent surgical debridement in combination with administration of intravenous antibiotics, intravenous immunoglobulins and inotropic support.

The intravenous antibiotics that were given on admission were benzylpenicillin, meropenem, metronidazole and clindamycin based on local microbiology advice. Urgent surgical debridement was undertaken.

In theatre, incisions were made to the lower eyelid. Necrotic fat and orbicularis oculi muscle were identified and debrided. An incision was also made in the upper eyelid with no necrotic tissue found at this site. The eye was surgically decompressed with a lateral canthotomy undertaken. Thorough irrigation was performed following debridement and regular application of chloramphenicol ointment thereafter. The patient attended ITU following surgery for inotropic support.

At second debridement, the following day, further necrosis of the orbicularis oculi and fat of the lower eyelid were identified and debrided. The intravenous antibiotic regimen was changed to linezolid, clindamycin and meropenem as advised by our microbiologist.

One week following admission, the patient underwent emergency endoscopic band ligation following variceal bleed and was managed supportively thereafter on the gastroenterology ward.

The debrided wound healed by secondary intention to leave a cicatricial ectropion of the right lower eyelid. This was corrected 6 weeks later by scar release and reconstruction with a full-thickness skin graft.

Outcome and follow-up

Follow-up oesophago-gastro-duodenoscopy was performed requiring six further variceal bands. Outpatient gastroenterology and plastic surgery follow-up were continued.

Discussion

NF is a rare soft tissue infection with a high mortality rate.¹ Early recognition and treatment are crucial to survival. The incidence of NF is around 500 cases per year within the UK.² NF can affect any part of the body, but the extremities, perineum and trunk are the most commonly affected.² Involvement of the face and periorbita is rare, theorised to be due to the excellent blood supply to the head and neck. Untreated, periorbital NF typically results in rapid tissue destruction and may lead to visual loss, usually 2–4 days following initial infection.³ The mortality rate, usually from multiorgan failure secondary to sepsis, is between 12% and 57%.^{4 5}

The aetiology of periorbital NF remains uncertain. It is seen mainly in adults, with a female preponderance (54%).⁶ The infection can follow local blunt trauma (17%), penetrating injuries (22%) and surgery to the face (11%), but in about one-third of cases (28%), no cause is identified.⁷ Most patients who develop NF have pre-existing comorbidities and immunosuppressive risk factors that render them susceptible to infection such as diabetes, malignancy (particularly leukaemia) and, as in this case, chronic hepatitis and liver cirrhosis, where there is a five to seven times higher incidence in these patients than other hospitalised patients.^{1 8} However, about one-half (47%) of patients are previously thought to be healthy and have no underlying medical condition, as was initially considered in our patient.⁶

The pathophysiology of NF relates to location, extension, thrombosis and ischaemia.

Due to anatomical differences, NF within the eyelid behaves differently to that at other sites. The skin of the eyelid is thin with no underlying subcutaneous tissue. The underlying orbicularis oculi muscle lies superficial to the fascia of the orbital septum and fat. The orbicularis oculi muscle has a rich blood supply, acting as a barrier between skin and periorbita, which prevents the spread of infection directly from skin into the orbit. The dermis of the eyelid is firmly attached both medially and laterally to the nasojugal and malar folds, respectively, creating a further barrier for the spread of infection. The easiest route for infection to spread is therefore across the nasal bridge to the contralateral lids, which may explain the high incidence of bilateral NF.⁹

Periorbital skin necrosis may be seen earlier than at other sites due to the thin nature of the skin here and may precede the spread of infection into the orbit. It is postulated that tissue necrosis occurs due to bacterial release of toxins that also contribute to systemic complications of acute kidney injury and septic shock. Intraorbital spread of infection occurs deep to the orbicularis oculi, along the orbital fibrous septae and blood vessels, potentially resulting in arterial occlusion and blindness.^{6 10} Thrombosis of these vessels is thought to result from direct bacterial invasion into the hypodermis, leading to tissue ischemia that is exacerbated by the presence of oedema. The local tissue ischemia promotes infectious dissemination and further necrosis.⁹

Possible effects of the underlying liver disease relate to immunodeficiency and systemic inflammation.¹¹ In cirrhosis, hepatic immune surveillance function and synthetic liver function are impaired, negatively affecting systemic immune cell functioning.¹² Liver cirrhosis is hence known to predispose to serious bacterial infections, with the incidence of infection five to seven times higher in these patients than in other hospitalised patients.¹³ Furthermore, cirrhosis results in systemic upregulation of proinflammatory pathways, and bacterial infections are in turn known to trigger acute decompensation in liver cirrhosis, as seen in this case.¹⁴ Decompensation is thought to result from translocation of bacteria via the intestino-portal route, the immune ‘barrier’ that is weakened in patients with liver cirrhosis. Bacteria present within the blood stream may then seed into oedematous soft tissue leading to NF, usually in the lower limbs.¹⁵ This case did not present with peripheral oedema, but it is possible that bacterial translocation and bacteraemia could have occurred, in the absence of trauma, via the weakened gastrointestinal immune defences with subsequent seeding of bacteria to the face.

The causative organism in periorbital NF is mainly group A β-haemolytic streptococcus (50%), occasionally in combination with Staphylococcus aureus (18%).⁶ This virulent organism has raised concern in recent years as a ‘toxic shock strain’ of streptococcus leading to fasciitis with organ dysfunction.² The intraoperative tissue specimen in this case also demonstrated Gram-positive cocci on microscopy, confirmed on culture to be group A streptococcus, with resulting organ dysfunction requiring inotropic support.

Hung et al report that the underlying liver disease may affect the bacteriology of NF, and hence the appropriate antimicrobial cover required. Monomicrobial infection of Gram-negative bacilli, B-haemolytic streptococci or S. aureus is frequently implicated.⁸ Additionally, studies have identified Vibrio vulnificus, a Gram-negative rod, in NF patients with chronic liver disease.⁸ The microbiological findings have not been reported to affect overall mortality but are an important consideration when commencing antimicrobial therapy.¹³ Importantly, Hung et al also identified that overall mortality rates of patients with liver cirrhosis and NF are higher than those reported in patients with NF alone.⁸

Although the incidence of hepatitis C is high, with around 1875 new cases per year, the presence of occult liver infection in this case is unusual. Hepatitis C is not commonly reported in the literature as an important risk factor for NF despite well-recognised immunological effects of chronic hepatitis C infection, namely reduced lymphocyte maturation and impaired peripheral activation and recruitment, with effects varying depending on the chronicity of infection.^15–17 However, this association has been described, first by Scher et al in 2012. Their study demonstrated a significantly greater incidence of hepatitis C in patients with NF (34%) compared with the general population (1.8%). Furthermore, they also report that concomitant hepatitis C infection in NF is of prognostic significance with a higher mortality rate of 30% compared with 21% for those without hepatitis C viral infection in their patient group.¹⁵

Notwithstanding the impact of concomitant disease, mortality rate from NF in patients with periorbital spread alone is high, with the prognosis known to be adversely affected by delay in diagnosis and treatment, and spread of infection from the face to the neck.⁴ Therefore, to aid prompt treatment, we outline the key clinical features and initial management options when presented with a clinical suspicion of periorbital NF below.

Clinical features of periorbital NF:

• Acutely painful and erythematous swelling of the eyelids and skin surrounding the eye, with oedema and blistering of the skin.

• Rapid onset of symptoms and the severity of pain not keeping with examination findings.

• Proptosis, restricted ocular motility and development of a relative afferent pupillary defect, suggestive of orbital involvement.

• Rapid progression of erythema to dusky cyanotic discolouration and serous fluid-filled bullae, indicative of the underlying necrosis seen in NF.⁸ This can distinguish periorbital NF from preseptal and orbital cellulitis.

• Inability of adequate antibiotic regimen alone to prevent progression of examination findings.

• Clinical systemic involvement: fever, tachycardia, hypotension.

• Laboratory findings: leucocytosis, raised CRP, raised lactate, acidosis, high LRINEC score.

Initial management of periorbital NF:

• Urgent intravenous antibiotic therapy and expedient surgical debridement are the mainstay of treatment. Imaging, although helpful, should not delay debridement.

• Initiation of broad spectrum antibiotics as early as possible. In our unit, we administered clindamycin, linezolid and meropenem.

• Early escalation and multidisciplinary involvement.

• Involvement of intensive care for resuscitation, stabilisation and systemic support.

Following initial resuscitation and management, thorough investigation of the possible source of infection, including any underlying predisposition or immunosuppression, is imperative. In this case, routine infective and liver screening, alongside ultrasound scanning, identified hepatitis C antibodies, decompensated liver failure and portal systemic compromise. Given the initial presentation in this case, in keeping with almost one-third of cases (28%) of periorbital NF where no local precipitant injury or underlying predisposing risk factor is identified,¹⁸ we advocate that once initial management is commenced, early screening into underlying co-morbidities is performed, including a non-invasive liver screen.

Our patient presents a number of interesting learning points. Diagnosis of NF relies on careful clinical assessment and a high index of suspicion. Initial resuscitation, debridement and investigation into any predisposing factors, such as liver disease, are paramount to achieve a positive outcome. Major morbidity may result in, including loss of vision, loss of function and dissatisfaction with cosmesis.¹⁸ Mortality remains high, particularly in cases of delayed presentation, and is increased in concomitant liver disease. Therefore, these cases require a multidisciplinary approach to management. Our case involved input from plastic surgeons, intensivists, microbiologists, ophthalmologists and gastroenterologists. Multiple surgeries, including aggressive debridements and a challenging reconstruction, can be required, but the importance of investigation and management of underlying liver disease in this patient group must not be overlooked.

Learning points.

• Periorbital necrotising fasciitis (NF) can be challenging to differentiate from other pathologies; consider this diagnosis in a patient presenting with severe pain in the periorbita and systemic sepsis. Skin necrosis is a late sign.

• Early diagnosis, prompt surgical debridement and intravenous broadspectrum antibiotics under the care of a multidisciplinary team are critical for a good outcome.

• In a presumed fit and well patient, consider predisposing factors for NF including chronic liver disease.

• Hepatitis C not only predisposes to NF but may also confer a worse prognosis.