Introduction Necrotising fasciitis (NF) is a severe infection of deep subcutaneous soft tissues with high morbidity and mortality. Periocular necrotising fasciitis (PONF) is a very rare condition with many unanswered questions about the presentation and management. We present a retrospective case series of patients with PONF from three centres in Australia and two in the UK to investigate the clinical and microbiological characteristics and outcomes and report on patients treated with antibiotics alone.
Results Twenty-nine patients (20 men; 69%) with PONF were identified and followed up for between 2 months and 10 years (median 57, mean 52.6 months) between 1990 and 2013. Conditions associated with chronic immunocompromise were present in 16/29 (55%). Twenty-one (75%) recalled minor periocular trauma or an infected lesion, two having been assaulted by the same assailant. Systemic shock occurred in 6/29 (21%) patients and 1 died. Group A, β-haemolytic Streptococcus was the most common bacterium identified (25/29, 86%). Intravenous antibiotics were used in all patients, and up to five tissue debridements were required to control the disease in 23/29 (74%); reconstructive surgery was required in 12/29 (41%) patients. One patient died from the disease and visual loss occurred in four eyes of four patients (14%).
Conclusions PONF has a better prognosis than disease elsewhere in the body, but is still associated with significant risk of visual loss and a small risk of death. Intravenous antibiotic treatment with cautious observation may be reasonable in selected patients with a low threshold for debridement.
- Eye Lids
Statistics from Altmetric.com
Necrotising fasciitis (NF) is a severe necrotising infection of subcutaneous tissues that mainly affects the limbs or abdominal wall. Periocular necrotising fasciitis (PONF) is rare, with a recent study estimating a UK incidence of 0.24 cases per million per annum.1 Most experience of PONF, based on case reports and three small case series,2–11 indicates that PONF has a better prognosis than the condition elsewhere in the body, and there are reports of success with medical treatment alone.12 ,13 We present a series of patients with PONF to examine the clinical features, microbiological characteristics, disease course, management and outcomes for this rare condition.
Methods and patients
PONF is a clinical diagnosis and inclusion in this study necessitated a rapid spread of cellulitis through the subcutaneous periocular tissues, with early development of subcutaneous tissue necrosis.
A retrospective review of clinical case notes was performed for two cohorts of patients with PONF: ‘Cohort 1’ (14 patients) was drawn from experience of members of the Australia and New Zealand Society of Ophthalmic Plastic Surgeons (ANZSOPS), who were invited to contribute any cases of PONF since 2000; non-responders were emailed up to three times. ‘Cohort 2’ (15 patients) was derived from patients treated at Moorfields Eye Hospital, London, and Addenbrooke's Hospital, Cambridge, between 1990 and 2000.
The baseline data for each patient included age at presentation, gender, any history of preceding trauma (including burns or bites), systemic disease, smoking status and usage of alcohol, legal medications or illegal drugs. The presenting signs, disease course, management and any ocular or systemic complications were recorded. The microbiological, histopathological and radiological results were also collected.
Twenty-nine patients with PONF were identified. Their mean presenting age was 56 (median 57, range 21–95) and 20 (69%) were men. Conditions associated with chronic immunocompromise were present in 16/29 (55%): two with haematological malignancies (chronic myeloid leukaemia; myelodysplasia), six with long-standing diabetes (one bilateral lower amputee with severe microvasculopathy), six with chronic alcohol abuse (>56 units/week), one had diabetes as well), two with autoimmune diseases requiring immune-suppressing medication (ulcerative colitis with renal transplant: ciclosporin, azathioprine and prednisolone; chronic rheumatoid arthritis: non-steroidal anti-inflammatory drugs) and one with metastatic prostate cancer. A preceding injury was reported in 18/28 (64%) of patients in whom a history could be obtained (16 (57%) minor injuries, 2 (7%) surgical skin incisions) and preceding infection in 3/28 (11%) (one case of sinusitis (3.5%), one case of otitis externa (3.5%) and one lesion/vesicle (3.5%) on the glabella suspected of being herpes zoster). None of the cases of preceding trauma were due to insect or animal injuries. A further 5 (18%) patients were taking regular non-steroidal anti-inflammatory drugs (NSAIDs). Where data were available in 14 cases, injury occurred 1–14 days prior to the development of PONF, although the symptoms and signs developed rapidly in all patients (over 1–3 days).
All patients had severe periorbital cellulitis with skin breakdown and significant subcutaneous necrosis (figures 1 and 2). The area of inflammation involved the periocular area alone in 6 (21%) patients, other areas of the face including the other periocular area in 8 (28%), the neck or chest in 13 (45%), the scalp in 1 (3%) and in one (3%) case infection and inflammation spread intracranially. Other presenting ocular signs and symptoms included ptosis, proptosis with hypoglobus and systemic signs included severe pharyngitis, nausea and vomiting and headache. In the 10 cases in which we have the visual acuity at presentation, it was 6/9 or better in seven affected eyes and 6/36, count fingers and perception of light in one patient each. Systemic features were common; pyrexia in 17/29 (59%) and tachycardia in 9/14 in whom we have data for (64%). Six (21%) patients developed systemic shock, with 3/6 (50%) having pre-existing chronic diseases (myelodysplasia; alcoholic liver disease with diabetes; chronic myeloid leukaemia). One patient developed toxic epidermal necrolysis secondary to treatment, requiring admission to an intensive care facility.
Laboratory and radiological investigations
Where data were available, leucocytosis and raised serum C reactive protein levels (mean 258 mg/L; normal range <5 mg/L) were present in 13/14 cases. The average white cell count in this group was 19.3 (range 7.2–31.7, patient with myelodysplasia excluded). Group A β-haemolytic Streptococcus was isolated from periocular tissues or blood cultures in 25/29 (86%) of cases and in the other four patients Staphylococcus aureus (two cases), Streptococcus agalacticae (group B Streptococcus; one patient) and Pseudomonas aeruginosa (one patient) were cultured. Pus samples grew positive cultures in 23/29 (79%), tissue samples only 4/29 (14%), blood cultures only in 2/29 (7%). In the 13 CT scans in which a report was available, preseptal soft tissue swelling alone was present in 9 cases, mild orbital changes (mild lacrimal gland enlargement and/or mild anterior orbital fat stranding) in 3 cases and more marked orbital changes (superior rectus enlargement, widespread fat stranding and proptosis) with a locule of intracranial gas overlying the orbital roof in 1 case. Contrast enhancement of swollen preseptal tissue was noted in two cases.
Tissue necrosis was found in all 10 cases in which histopathological assessment is available. Non-granuloamtous, suppurative inflammation with neutrophil infiltration is described in several cases.
All patients received intravenous antibiotics (benzylpenicillin and flucloxacillin in the majority of the English cohort and a wide range of antibiotics in the Australian cohort), together with treatment for any underlying conditions and systemic shock. A range of 1–5 surgical debridements was performed in 23/29 (79%) patients (average two debridements in the Australia cohort) and 1 patient (with myeloid leukaemia and toxic shock syndrome) died prior to planned surgical intervention. All cases that underwent debridement demonstrated significant necrosis of the subcutaneous tissues. Debridement removed all necrosed tissue until healthy, bleeding tissue was reached. In Cohort 1, initial debridement was undertaken 1–14 days (mean 6.5 days) after presentation—that is, 1–23 days after onset of symptoms—and the average inpatient stay was 16 days (range 5–46 days). There was no association between the time taken for the first debridement and the final number of debridements required. One patient received four sessions of hyperbaric oxygen treatment in addition to three debridements. One patient aged 95 with chronic myeloid leukaemia was managed palliatively (and was the only patient who died from the disease) and did not undergo debridement. A further five (17%) patients’ disease was controlled with antibiotics alone, using the following combinations of antibiotics intravenously until clinical signs and laboratory markers of improvement were observed: (1) flucloxacillin and rifampicin; (2) vancomycin, meropenem and clindamycin; (3) benzylpenicillin and flucloxacillin; (4) benzylpenicillin and gentamicin; (5) benzylpenicillin, flucloxacillin and metronidazole. The clinical and laboratory ‘plateauing’ occurred after 2–3 days in one patient leaving two areas of slowly recovering necrosis in the upper lid and at 6 days in another patient by after development of extensive soft tissue swelling but necrosis restricted to the upper lid alone (timecourse data unavailable for other three medically treated patients). There were no apparent premorbid differences in these patients to those who did undergo debridement: three were men, three had immune-compromising conditions or differences in presenting disease severity: two had cellulitis of the lids only, but three had more extensive disease and one patient developed systemic shock, or in the bacteria cultured: group A Streptococcus and the other S. aureus. However, the clinicians were contacted in each case and reported a slowing and then stalling of the enlargement of both the necrotic area and the wider erythematous area as well as a plateau in the inflammatory marker levels. Visual loss occurred in four eyes of four patients (14%); three of these occurred during the acute illness and one later from exposure keratopathy. No patient suffered bilateral visual loss. Late reconstruction of the eyelids was required in 12/29 (41%) patients.
PONF has a much better prognosis for morbidity and mortality as compared with the condition elsewhere. One of 29 (3%) of our patients died and 6/29 (21%) developed systemic shock, as compared with an amputation risk of 16%, septic shock risk of 40% and a mortality of 22% (up to 67% in one study) for disease elsewhere.1 ,14–16 Systemic NF often requires at least 5 sessions of debridement to control and up to 33 sessions have been reported.17 In the present series, although early surgical treatment is often used to control the disease, it was treated with antibiotics alone in 5/29 (17%) cases. The retrospective nature of this and other studies does not allow conclusions on which will progress to greater morbidity without debridement and which can be managed conservatively. There were no apparent differences in risk factors or disease severity in our five conservatively managed patients. However, prompt slowing and then stabilisation was seen on close observation of the both the area of broken skin with underlying necrosis and the surrounding area of erythema, pulse, temperature and inflammatory markers. It is possible that other cases could have been managed conservatively, but debridement was undertaken in line with widespread opinion to remove all necrotic tissue. Hence, we may consider cautious observation in selected cases in which the clinical picture and inflammatory markers plateau with medical treatment, but with a low threshold for debridement. It is possible that hyperbaric oxygen may support conservative management, but no conclusions could be drawn from the one case in which hyperbaric oxygen was used concurrently with debridement in our series. Several reasons probably underlie the better prognosis for PONF: (a) earlier presentation, PONF arising in the most visually evident area, leading to short period of symptoms; despite the visual evidence, some patients in this series were not identified as being PONF until some days after presentation; (b) better antibiotic penetration, the very rich subcutaneous vasculature of the periocular tissues facilitating antibiotic delivery into affected non-necrotic tissues, and this might have allowed disease containment in a significant number (7/29) of cases. Three other cases of non-surgically treated PONF have recently been described12 ,13; (c) orbital septal integrity, the orbital septum appearing to retard posterior spread of PONF: infection appears to prefer spread along the superficial planes across the face, and thereby might limit the space for potential necrotic cavity formation.
Distinguishing NF from severe cellulitis can be difficult. NF is diagnosed clinically by the presence of necrotic tissue in addition to severe cellulitis. Necrotic tissue was seen in all patients in our series in whom we had histopathological assessment of tissue, and was clinically evident in those patients in whom debridement was not undertaken. Accordingly, we would consider early tissue biopsy (taken from the spreading edge of the lesion rather than the centre) in all patients with diagnostic uncertainty. Various bacteria can be gas forming in different settings, and subcutaneous air is described both clinically and radiologically in cases of NF. In our series, gas was only noted on CT imaging in one of the 14 patients in which we have CT reports and is therefore not a sensitive diagnostic sign, although it may be more evident on MRI scanning. However, CT is useful for determining the extent of spread of swollen tissue and particularly if there has been postseptal extension. There are also several other supporting clinical, laboratory and radiological features that may support the diagnosis, that were not collected in this study due to its retrospective nature: severe pain out of keeping with the clinical signs, woody induration and crepitus and eventual development of a dusky/purple hue.
As with NF at other sites, PONF is more common in men (68% this series; 17/23 (74%) in previous series3 ,5 ,8), which might be attributable to more frequent minor, contaminated skin trauma. The predilection of NF for minor trauma, rather than major injury, might occur because of the reduced ‘first-aid’ cleansing that occurs with minor injuries and the later subcutaneous sequestration of bacteria. Patients with chronic systemic disease or immunosuppressing medications are at greater risk of PONF probably because of impaired, neutrophil chemotaxis, phagocytosis and bactericidal activity against gram-positive cocci.18 A similar risk factor profile was found in the British Ophthalmic Surveillance Unit (BOSU) study, in which 12/30 patients had immune-compromising conditions or chronic medications.1
Our mortality rate (3%) is of the same order as other studies or PONF, with 10% in the BOSU study and 8.5% in a literature review of 94 cases.19 Notably—possibly because of a bias of case recall—smaller case series tend to report higher morbidity with septic shock in 4/7 patients (and one death) in one series and 1/11 death, and a further 1/11 unilateral visual loss through central retinal artery occlusion in another series.3 ,5
NF has been divided into two types—‘Type 1’ being a polymicrobial infection with anaerobic and aerobic bacteria in patients with immunocompromise or patients with chronic disease, and ‘Type 2’ being caused by group A Streptococci (GAS).14 It is possible the rates of Type 1 disease might be overestimated, as large areas of necrotic tissue would reasonably be expected to become rapidly populated by a wide spectrum of aerobic and anaerobic bacteria. GAS have a range of molecules that confer infective advantages, including surface M proteins that suppress neutrophil phagocytosis, and exotoxins A and B that stimulate cytokine release causing shock, organ failure and immune suppression.1 ,14 All but four of our series had GAS isolated. Group A Streptococcus was found in most patients within the BOSU study (22/29 cases).1 A range of broad-spectrum antibiotic regimens were used in our series. Most guidelines are not didactic, but advocate penicillin G and clindamycin if GAS is suspected or confirmed, although cover for gram-negative bacteria (eg, gentamicin) may be advisable before the organism is known.20
Despite PONF being rare, two of our patients (unrelated) developed the condition after being attacked by the same assailant, while in separate carriages on a train. Although neither bacterial subtyping from the patients nor cultures from the assailant were available, both patients did isolate GAS from their affected tissues. This extraordinary scenario might suggest that there could be more virulent subtypes of GAS that are particularly liable to cause NF.
Retrospective analyses of this study might be affected by recall bias. However, the rarity and severity of cases of this disease is likely to reduce the likelihood of omissions. Despite the case series combining two groups from different continents, the clinical features of the two cohorts are very similar.
PONF has better prognosis than NF elsewhere, but is still is associated with a significant risk of loss of vision (14%) and death (3%). Therefore, while it appears some cases may respond to medical treatment alone, the criteria for intervention in the form of debridement and the extent of such debridement remain unclear. In the absence of extensive disease and a systemically well patient, it may be reasonable to observe the response to intravenous antibiotics over the course of a 48 h period. However, clinicians should approach this path of management cautiously and have a low threshold for debridement in the event of progression.
Two of the cases in this paper have been part of a prior publication.12
Contributors SNR: conception and design of work, acquisition of data, analysis of data, interpretation of data, drafting of work, final approval of published version and agreement of accountability for all aspects of the work. ECF, ASH, KS, JMU, AAM, CR, TJS: design of work, acquisition of data, revising of work, final approval of published version and agreement of accountability for all aspects of the work. GER and DS: conception and design of work, acquisition of data, revising of work, final approval of published version and agreement of accountability for all aspects of the work.
Funding GER acknowledges support from the National Institute for Health Research (NIHR) Biomedical Research Centre based at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology.
Competing interests None declared.
Patient consent Obtained.
Ethics approval Ethical approval was received from the Royal Adelaide Hospital Research Ethics Committee.
Provenance and peer review Not commissioned; externally peer reviewed.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.