Stephanie Ming Young
Stephanie Ming Young received her Bachelor of Medicine and Bachelor of Surgery degrees from the National University of Singapore (NUS). She completed her basic and advanced ophthalmology training in National University Hospital and Singapore National Eye Centre, and went on to subspecialize in ophthalmic plastic and reconstructive surgery. She won the Gold Medal and Book Prize in Ophthalmology and received a Distinction Award for Ophthalmology-related research for her Undergraduate Research Opportunities Program in medical school. Since then, she has won several ophthalmology-related awards and grants, as well as published various papers on the subject in peer-reviewed journals. Aside from clinical work and research, Dr. Young is a clinical lecturer with the NUS Clinical Faculty Scheme and teaches medical students as well as junior doctors. She strongly believes in giving back actively to society and sits on the executive committee of Singapore Women’s Association, where she runs monthly free eye screening events for the community as part of the Singapore Visioncare Programme. She has also participated in many cataract and Oculoplastic trips to remote areas in need of eye care in various countries around the world.
Seah Lay Leng
Professor Seah is one of the few pioneers in the Oculoplastic and Orbit sub-specialty. She is recognized for her contribution to the establishment and the development of the Oculoplastic Department, Orbit and Ophthalmic Prosthetic departments in the Singapore National Eye Center and Pediatric Oculoplastic in the Kandan Kabau Women’ and Children’s Hospital in Singapore. She received her fellowship training in Oculoplastic Surgery at the London Moorfield’s Eye Hospital, UK and Orbital Surgery Centre at the Vancouver Eye Center in Canada. In recognition of her contribution to the development of Orbit sub specialty at the Singapore National Eye Center and the region, she was elected to be a member of the “Orbit Society” in 2008 organized by the International Orbital Surgeons. She is also a board member of the prestigious International Thyroid Eye Disease Society (ITEDS).
Professor Seah is particularly active in medical education for undergraduate and post-graduate medical students of the National University of Singapore and has been a mentor for many local and overseas fellows for advanced fellowship training in Oculoplastic Surgery. Her international participation includes numerous presentations as an invited speaker. She had held the chair in regional and international conferences and the chair of organizing committee of regional and international orbital symposia and oculoplastic workshops
Introduction
Group A beta-hemolytic Streptococcus is one of the most common human pathogens [1]. It is a gram-positive bacterium responsible for a wide range of both invasive and noninvasive infections [1, 2]. They are known to cause three overlapping clinical presentations: toxic shock syndrome, necrotizing fasciitis, and bacteremia with no identifiable focus [2].
Necrotizing fasciitis is a rapidly progressing and potentially fatal infection that spreads along subcutaneous tissue planes and is associated with high morbidity and mortality [1]. Necrotizing fasciitis has also been referred to as hemolytic streptococcal gangrene, Meleney ulcer, acute dermal gangrene, hospital gangrene, suppurative fasciitis, and synergistic necrotizing cellulitis.
The frequency of necrotizing fasciitis has been on the rise because of an increase in immunocompromised patients with diabetes mellitus, cancer, alcoholism, vascular insufficiencies, organ transplants, HIV infection, or neutropenia. The estimated annual incidence of these infections is 3 cases per 100,000 people, with about 10,000 cases occurring each year in the United States [3, 4]. There may be an increased incidence in African and Asian countries; however, because of the lack of recorded cases, the true incidence is not known. Overall mortality is estimated to be from 10 to 15 % [4, 5].
While it usually involves the extremities, abdominal wall, and groin, about 10 % of cases may affect the head and neck region [4–6]. Necrotizing fasciitis may sometimes, although rarely, involve the eyelids, with approximately 65 well-documented case reports over the last 50 years [4, 5, 7–44]. Necrotizing fasciitis has a different clinical course in the eyelids than elsewhere in the body due to the thin eyelid skin with a rich blood supply harbored by the orbicularis oculi muscle, which lies superficial to the orbital septum fascia and fat. This allows the skin infection to become noticeable earlier, while spread occurs deep to the orbicularis oculi muscle. In addition, by behaving as a vascularized barrier between the skin and underlying infected tissues, the orbicularis oculi muscle also may act to preserve more skin to spare the eyelid margins from necrosis in most cases [4]. However, in all cases orbital involvement may lead to vision loss, and failure to recognize periocular necrotizing fasciitis can lead to severe ocular morbidity and even loss of life, if facial, cervical, or intracranial extension occurs [5].
Overview
Classification
Different terms and classifications have been used to describe necrotizing infections of the skin and subcutaneous tissue. Historically, necrotizing infections were classified according to anatomical sites. Fournier gangrene (involving the perineum) and Ludwig angina (involving submandibular and sublingual spaces) are examples. These infections were named after the physicians who first described them. Other names which necrotizing fasciitis has been known by include synergistic necrotizing cellulitis, streptococcal myonecrosis, and gas gangrene. While many terms have been used to describe necrotizing soft-tissue infections, a few distinct necrotizing fasciitis syndromes should be recognized. The causative bacteria may be aerobic, anaerobic, or mixed flora [45]. Three most important types and their associated causative organisms are as follows:
- 1.
Necrotizing fasciitis type I: Mixed anaerobes, gram-negative aerobic bacilli, enterococci
- 2.
Necrotizing fasciitis type II: Group A Streptococcus
- 3.
Necrotizing fasciitis type III or gas gangrene: Clostridial species (C. perfringens, C. histolyticum, C. septicum)
Etiology
Predisposing factors for the development of necrotizing fasciitis due to group A Streptococcus (Streptococcus pyogenes) include varicella, penetrating injuries, minor cuts, burns, splinters, surgical procedures, childbirth, blunt trauma, and muscle strain [1, 48]. Surgical procedures may cause local tissue injury and bacterial invasion, resulting in necrotizing fasciitis, as can intramuscular injections and intravenous infusions. Similarly, minor insect bites may set the stage for necrotizing infections as Streptococci are introduced into the wounds. Illnesses such as diabetes or cancer have been described in over 90 % of cases of progressive bacterial gangrene. Host defenses can be compromised by underlying systemic diseases favoring the development of these infections. In addition, local ischemia and hypoxia can occur in patients with systemic illnesses (e.g., diabetes) [1–3, 6, 7, 49]. Of patients with necrotizing fasciitis, 20–40 % are diabetic, a condition primarily affecting the microvascular circulation. Contact with an infected person may be associated with secondary infection, though such cases are uncommon. The patient’s use of nonsteroidal anti-inflammatory agents may delay diagnosis by attenuating the cardinal manifestations of inflammation. Furthermore, because such agents impair phagocytic function and alter the host’s humoral immune responses, a minor infection may develop into a fulminant one [48, 50, 51]. It has also been reported that patients with invasive streptococcal infections are prone to them because they have low antibody titers directed to the bacterial exotoxins or membrane M proteins [52].
Presentation
History
Diagnosis of necrotizing fasciitis can be difficult and requires a high degree of suspicion. Risk factors described above should be identified. Outcome depends on prompt recognition and early treatment. Delayed diagnosis and treatment are associated with higher morbidity and mortality.
Patients with necrotizing fasciitis present with the history of acute periorbital swelling associated with severe pain. The overlying skin is initially red, tense, and swollen. The hallmark symptom of necrotizing fasciitis is intense pain and tenderness over the involved skin and underlying muscle, as the infection spreads subcutaneously along fascial planes [4, 53]. This severe pain may frequently present before the patient develops systemic features (high fever, chills, rigors, sweating), and the pain may be out of proportion to physical findings. As it is a rapidly progressive condition, the skin may become cyanotic and blue gray within 1–2 days, with irregular erythematous borders [2, 21]. Within 4–5 days, frank cutaneous gangrene usually develops, followed by sloughing of the skin due to underlying suppuration by 8–10 days [2, 21, 22] (Fig. 36.1). In the later stages, the area involved becomes anesthetic from the destruction of the cutaneous nerves [54, 55]. The patient may be toxic and in later stages may have signs of multi-organ failure or disseminated intravascular coagulation [54].
Fig. 36.1
Young boy presenting with left periorbital necrotizing fasciitis. The periorbital skin is erythematous, edematous, and tender. There is also evidence of cutaneous gangrene and sloughing of skin, signs that should alert the physician to an ongoing necrotizing process
Physical Examination
Physical findings may not be commensurate with the degree of patient discomfort. Early in the disease course, the patient may look deceptively well; unfortunately, this may interfere with early detection, which is key to a favorable outcome. Soon, however, the patient will usually begin to appear moderately to severely toxic.
The infection begins with swelling and redness over the periocular region. The skin over the swelling appears erythematous and can be mistaken for erysipelas. The redness quickly spreads, and its margins move out into normal skin without being raised or sharply demarcated. As the infection progresses, the skin near the site of insult develops a dusky or purplish discoloration. The disease progresses rapidly, and the lesion may turn gangrenous within 24 h [55]. At this stage, the skin shows violaceous discoloration, and fluid-filled bullae appear on the skin, which helps to distinguish it from preseptal cellulitis. The initial necrosis appears as a massive undermining of the skin and subcutaneous layer (Fig. 36.2). If the skin is open, gloved fingers can pass easily between the two layers and may reveal yellowish-green necrotic fascia. The normal skin and subcutaneous tissue become loosened from the rapidly spreading deeper necrotic fascia that may be some distance away from the initiating wound. The subcutaneous tissue involvement is more extensive than the involved overlying skin. In the later stages, the area involved becomes anesthetic, caused by thrombosis of the subcutaneous blood vessels, leading to necrosis of nerve fibers [54]. There can be crepitus on palpation, which may be seen as air in the soft tissue on X-ray [56]. Without treatment, secondary involvement of deeper muscle layers may occur, resulting in myositis or myonecrosis. Normally, however, the muscular layer remains healthy red with normal bleeding muscle under the yellowish-green fascia. In summary, the most important signs are tissue necrosis, putrid discharge, bullae, severe pain, gas production, rapid burrowing through fascial planes, and lack of classical tissue inflammatory signs. The patient may be toxic and in later stages may have signs of multi-organ failure or disseminated intravascular coagulation [54, 55].
Fig. 36.2
Patient with fulminant periorbital necrotizing fasciitis. On examination there is significant periorbital swelling and erythema, sometimes (as in this case) extending to the lower cheek and face. There is sloughing of the preseptal and pretarsal skin, with areas of necrosis and eschar formation. The violaceous to blackish skin discoloration and fluid-filled bullae help to distinguish it from preseptal cellulitis
Clinical Course
As mentioned above, necrotizing fasciitis has a different clinical course in the eyelids than elsewhere in the body due to the thin eyelid skin with a rich blood supply harbored by the orbicularis oculi muscle, which lies superficial to the fascia of the orbital septum and fat. This allows the skin infection to become noticeable, usually less than 3 days from onset of symptoms [4]. The necrosis of the skin occurs rapidly, and as a result, the lids are unlikely to harbor the smoldering nidus of infection [41]. In addition, the orbicularis oculi muscle contains the eyelid marginal arterial arcades, whose perfusion serves to spare the eyelid margins from necrosis in most cases, even in cases of deep orbital involvement [4]. Lastly, the dermis is attached firmly at the nasojugal fold medially and to the malar fold laterally, forming a firm adhesion that prevents the spread of inflammation. Of reported cases of periorbital necrotizing fasciitis, 45 % had bilateral involvement and 55 % had unilateral involvement [5, 7–44]. The reason that necrotizing fasciitis may involve both eyes is because of the little resistance provided by the subcutaneous tissue over the nose to the spread of infection.
Necrotizing fasciitis of the eyelids has a reported mortality rate of 8.5–14.2 % and is attributable to systemic complications like septicemia, shock, and multi-organ failure [55]. This reported rate is lower than that of other body site involvement (28–32 %) [3, 5, 55]. This may be due to earlier recognition and treatment of infection in this area, compared to infection of the lower half of the face, with the latter having a higher risk of spread to the vital structures of the neck and thoracic cavity.
However, periocular necrotizing fasciitis has a high morbidity especially in cases of orbital involvement with vision loss [4, 28, 57]. It can cause deep orbital involvement by spread of the infection along the orbital fibrous septae and blood vessels, resulting in arterial occlusion and blindness [4]. Development of retinal artery occlusion is due to severe perivascular involvement causing thrombosis, which may be accentuated by systemic hypercoagulability, increased fibrin deposition, and fibrinolysis in patients with necrotizing fasciitis [58, 59]. In addition, increased intraorbital pressure due to severe inflammation and edema of the periorbital tissues may also contribute to ischemic necrosis and development of arterial occlusion.
Differential Diagnosis
Differential diagnoses of periorbital necrotizing fasciitis would include any infectious or inflammatory processes affecting the eyelids, eye, and orbit [60]. Infectious possibilities (in increasing degree of severity) include blepharitis, conjunctivitis, preseptal cellulitis, orbital cellulitis, endophthalmitis, cavernous sinus thrombosis, and rhino-orbital mucormycosis [34, 44]. In particular, necrotizing fasciitis may be difficult to distinguish from preseptal or orbital cellulitis. However the former will show signs of rapid progression and subsequent cyanosis of involved tissue and formation of serious fluid-filled bullae, which will not be found in the more common non-necrotizing cellulitis [60–64].
Noninfectious differentials would include orbital pseudotumor, rapidly growing orbital tumor, Graves’ disease, and subperiosteal hematomas [60–64]. However, fever would typically be absent for most of these entities. Similar to the infectious differentials, these entities would not show presence of bullae and violaceous discoloration and necrosis of the skin, which would point toward the diagnosis of necrotizing fasciitis [55, 65].
Workup
The diagnosis of necrotizing fasciitis is mostly made on the basis of clinical features. Laboratory tests, along with appropriate imaging studies, may facilitate the diagnosis of necrotizing fasciitis [66].
Laboratory Investigations
A complete laboratory evaluation should include the following: complete blood count with differential, serum chemistry studies, arterial blood gas measurement, urinalysis, as well as blood and tissue cultures. Numerous parameters have been shown to relate significantly to the severity of NF and subsequent death [67–72]: white cell count over 15,000/μl or less than 4,000/μl, more than 10 % neutrophils, platelet count below 100,000/μl, abnormal coagulation (activated partial thromboplastin time over 60s, international normalized ratio more than 1.5), serum creatinine concentration over 2.0 mg/dl, raised liver enzyme levels, C-reactive protein concentration exceeding 13 mg/dl, and creatinine kinase level over 700 units/l.
Imaging
The presence of gas in the soft tissue on plain radiographs has been reported, but has been found to have no value in the diagnosis of necrotizing infections and may even hinder the diagnosis with consequent increased morbidity and mortality [73–75].
Bedside ultrasonography may be useful in patients with necrotizing fasciitis, as it may reveal subcutaneous emphysema spreading along the deep fascia, swelling, and increased echogenicity of the overlying fatty tissue with interlacing fluid collections [76, 77].
Computer tomography (CT) scan and magnetic resonance imaging (MRI) are extremely useful in making an early diagnosis and can serve as a guide to surgical debridement [69] (Fig. 36.3). Both modalities can detect the extent of necrotizing fasciitis and identify soft-tissue edema infiltrating the fascial planes many hours prior to the appearance of cutaneous signs. The characteristic CT findings of necrosis with asymmetric fascial thickening and the presence of gas in tissues help to differentiate necrotizing fasciitis from cellulitis, myonecrosis, and phycomycosis [68]. MRI is useful in detecting soft-tissue infection with its unsurpassed spatial resolution, multiplanar capabilities, and soft-tissue contrast and sensitivity in detecting soft-tissue fluid [78–80]. Absence of gadolinium contrast enhancement in T1-weighted images reliably detects fascial necrosis in patients requiring operative debridement, while T2-weighted images may show well-defined regions of high signal intensity in the deep tissues.
Fig. 36.3
Computer tomography (CT) findings of necrosis with asymmetric fascial thickening and the presence of gas in tissues correlate with the picture of necrotizing fasciitis seen in Fig. 36.1
Microbiology
In a systematic review by Goh et al., the overall rates of positive wound and blood cultures were 76.5 % and 36.2 %, respectively, in patients with necrotizing fasciitis [72]. Organisms common in polymicrobial infections were Staphylococcus spp., Streptococcal spp., Bacteroides, and Escherichia coli [81–85]. Organisms found in monomicrobial infections were Streptococcus pyogenes and Staphylococcus aureus [71, 86]. Marine bacteria (Vibrio spp., Aeromonas spp., and Shewanella spp.) were causal organisms in several studies from Korea and Taiwan, which have extensive coastal areas where these marine bacteria thrive in [70, 71, 87].
Treatment
Once the diagnosis of necrotizing fasciitis is confirmed, treatment must be initiated without delay. Because of the complexity of this disease, aggressive multidisciplinary treatment is mandatory to avoid morbidity (e.g., severe permanent disfigurement, loss of vision, exenteration) and mortality linked to misdiagnosis or delay in diagnosis [82]. Hemodynamic parameters should be closely monitored and aggressive resuscitation initiated immediately if needed to maintain hemodynamic stability. The patient should ideally be admitted to a surgical intensive care unit where the surgical staff is skilled in performing extensive debridement and reconstructive surgery.
Early recognition and initiation of high-dose antibiotics combined with tissue debridement help to decrease the mortality. There has been literature documenting successful nonsurgical management of group A Streptococcus eyelid necrotizing fasciitis [41, 88–90] (Fig. 36.4). However, while milder cases may respond to antibiotic therapy alone, because of the thrombosis of the blood vessels, antibiotics may not reach the infected site. Therefore, antibiotic therapy has to be combined with prompt surgical debridement of the affected tissue. By decreasing bacterial load and hyaluronic acid production, surgical debridement limits bacterial dissection through connective tissue and decreases the production of pyogenic exotoxins [4, 89].
Fig. 36.4
Patient on admission (above) and at 5 months after treatment (below), after skin reconstructive surgery was carried following resolution of acute infection. This patient showed marked clinical and cosmetic improvement with intravenous antibiotic therapy alone, suggesting that selected cases of uncomplicated eyelid necrotizing fasciitis can be treated conservatively with good results
Intravenous antimicrobial therapy is indicated in all patients with necrotizing fasciitis. The broad-spectrum antibiotics initiated should be effective against beta-hemolytic Streptococcus (principally S. pyogenes) and other organisms that may be involved in the pathogenesis of necrotizing fasciitis of the eyelids [60]. Although S. pyogenes is the bacterium most frequently involved in periorbital necrotizing fasciitis, the microbiology of the infection cannot often be predicted accurately before final identification of organism on wound culture. Hence, empirical antimicrobial therapy should consist of beta-lactam antibiotics, such as penicillin or cephalosporin and clindamycin [2, 3, 91, 92]. Penicillin is effective against group A beta-hemolytic Streptococcus. Addition of protein synthesis inhibiting antibiotics like clindamycin has a favorable outcome. It decreases the production of streptococcal toxins and enzymes even at subinhibitory concentration [93]. Type 1 necrotizing fasciitis (polymicrobial) requires the addition of aminoglycosides and⁄or metronidazole.
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