Periocular necrotizing fasciitis is extremely rare: a review by Amrith et al. [2] traced 94 cases reported in the literature between 1991 and 2012. Median age was 46. One-third of the cases were bilateral. A review by Lazzeri et al. [4] collected 104 published reports of periorbital necrotizing fasciitis between 1950 and 2008. In this review, ages ranged from 17 months to 93 years, with an average age of 50 years. Both reviews indicated a slight male predominance. In a prospective BOSU study [5] conducted in the United Kingdom, Flavahan et al. found 30 new cases of periocular necrotizing fasciitis in a two-year period between 2010 and 2012, indicating an incidence of 0.24 per million per annum.

Necrotizing fasciitis is caused by soft tissue infection that leads to liquefactive necrosis and extensive soft tissue destruction [5]. The infection and the inflammatory response spread horizontally along the avascular fascial planes, invariably leading to ischemic necrosis of the skin [2]. The superficial avascular musculoaponeurotic system (SMAS) is usually the fascial plane involved first. At this level, resistance to bacterial spread is poor, allowing the process to rapidly extend. When the infection penetrates the fascia, it spreads along longitudinal muscle bundles. Collagenase and hyaluronidase, released from bacteria, aid in bacterial invasion and contribute to aggressive tissue damage. Polymorphonuclear leucocytes infiltrate deep tissues, causing thrombosis of nutrient vessels and suppuration of veins and arteries passing through the fascia [5]. This is accompanied by gangrene of subcutaneous fat and dermis. Bullae and vesicles can be seen, followed by occasional ulceration of the skin. Muscles, bone ligaments, and tendons are usually spared. The process may be limited and localized, or it may evolve into fulminant and have a devastating course. Bacterial toxins that spill into the blood may lead to systemic toxicity and inflammatory response. If prompt medical and surgical treatments are delayed, necrotizing fasciitis often leads to sepsis, organ failure, and eventually death.

Periorbital necrotizing fasciitis may be the result of superficial infection that enters the subcutaneous plane, or it can arise from deep soft tissue infection that spreads along fascial planes without interference of the overlying skin [4].

A history of previous penetrating injury or abrasion is the most common etiology for periorbital necrotizing fasciitis, reported in 20–30% of cases [4, 5]. A specific alert should be noted in cases of eyelid lacerations sealed with tissue adhesives in children. When appearing as a rapidly occurring periorbital cellulitis (approximately 24 h following the injury), it may evolve into life-threatening necrotizing fasciitis and close observation is mandatory [6] (see case persentation later in this chapter).

Other possible etiologies are blunt trauma, reported in up to 17% of cases [4], history of surgical procedure such as blepharoplasty, dacryocystorhinostomy, surgical biopsy or excision, and self-puncture of hordeolum externum in approximately 10% [4, 5]. Retrobulbar injection was reported as a rare but potential etiology for necrotizing fasciitis involving both the orbital and periorbital structures [7]. Periorbital necrotizing fasciitis may also develop after human or insect bites or tooth extraction [4]. Dental infections are the most common cause for head and neck-necrotizing fasciitis [8] and may spread to the periocular area. Upper respiratory tract infection such as pharyngitis can also comprise the source for pathogen spread.

Systemic immunocompromising conditions such as diabetes, alcoholism, rheumatic diseases, HIV infection, chemotherapy, long-term steroid therapy, and immunosuppression are considered predisposing factors to necrotizing fasciitis but are seen in only about half of cases [4].

In general, necrotizing fasciitis has been categorized based on the causative organism: type I is caused by mix of anaerobes, gram-negative bacilli, and enterococci. Type II is caused by group A streptococci, occasionally with coexisting staphylococcal involvement [4]. Necrotizing fasciitis of trunks and extremities tends to be a polymicrobial infection, with up to 11 organisms being isolated in a single case [3]. In contrast, the most commonly reported microorganism associated with periorbital necrotizing fasciitis is β-hemolytic Streptococcus. This has been cultured in up to three quarters of cases and is usually the sole and very lethal pathogen [4, 5, 9, 10]. Most reports indicate it as a risk factor for death in periorbital necrotizing fasciitis cases. The virulence of group A streptococcus is attributed to a wide range of factors, both cell associated and secreted, which interact with human inflammatory cells and mediators to promote the pathogen survival and distribution [11]. Membrane-bound antigens, such as M-protein and fibronectin-binding proteins, inhibit antibody-mediated phagocytosis and enable bacterial adherence to host cells and tissue. Exotoxins such as superantigens and proteases support bacterial spread and invasion and facilitate inflammatory response. There are several strains of superantigens, which are considered fundamental for the pathogenesis of streptococcal toxic shock syndrome and the fatal course of necrotizing fasciitis [11].

Staphylococcus is present in up to one quarter of cases and is usually seen as coinfection with β-hemolytic Streptococcus. Pseudomonas aeruginosa is the second most common pathogen that causes periorbital necrotizing fasciitis as a single agent [2]. Moraxella catarrhalis, Staphylococcus albus, Streptococcus viridans, Propionibacterium acnes, Citrobacter, enterococci, and Serratia are less common causative agents. Cryptococcus neoformans, candida, and aspergillus are rare and seen mainly in immunocompromised patients [2, 4].

Differential diagnosis of periocular necrotizing fasciitis is listed in Table 9.2. Contact dermatitis is the most common inflammatory process involving the eyelids [12]. Thin and exposed skin allows for penetration of both contact and airborne allergens. The eyelid skin is typical site for the use of cosmetics. Proximity to the eyes makes this sensitive skin susceptible to the toxic and allergenic effect of ocular topical medications and contact lens solutions.

Erysipelas is a bacterial skin infection of the dermis and superficial cutaneous lymphatics, more common in the face. It appears as a tender, erythematous, indurated, and tense shiny plaque. The borders of the lesion are typically sharply raised, defining the demarcation between the affected and healthy skin. Most cases are caused by group A streptococci, and the age groups most affected are children and elderly between the ages 60–80. Erysipelas may cause gangrene or abscesses but also systemic complications such as pneumonia, glomerulonephritis, endocarditis, and toxic shock syndrome. Flat erythema, crepitus, rapid progression to frank necrosis, and relative resistance to treatment can aid in differentiating between necrotizing fasciitis and erysipelas.

Orbital cellulitis and preseptal cellulitis tend to a much more indolent course, although both may be hard to differentiate from orbital necrotizing fasciitis in its initial presentation. Orbital cellulitis may exhibit systemic manifestations such as fever and septic shock. Devastating neurological complications in orbital cellulitis may be confused with complicated necrotizing fasciitis, including ophthalmoplegia, optic nerve dysfunction, meningitis, and alterations in consciousness in cases of sinus vein thrombosis.

Nonspecific orbital inflammation is an inflammatory condition which involves the periorbital and orbital region. Frequently bilateral, it may cause swelling, redness, pain, and an ocular motility disturbance which may mimic orbital necrotizing fasciitis. It is noninfectious and usually responds rapidly to steroid treatment. Recurrent episodes are not uncommon.

Blepharochalasis is a rare syndrome, characterized by recurrent episodes of painless eyelid edema, eventually leading to thinning, wrinkling, and discoloration of the eyelids with redundant skin and eyelid malposition. The upper eyelids are more commonly affected, and most cases are bilateral. The cause is unknown, but a hereditary form of the disease exists. Some reports pointed out a preceding period of physical or emotional stress.

The typical malar rash of systemic lupus erythematous (SLE) symmetrically involves the cheeks and the nasal bridge but spares the nasolabial folds and is occasionally painful. It lasts from days to weeks but usually does not spread beyond the cheeks and remains within the erythematous-pruritic range.

Cavernous sinus thrombosis usually follows sinusitis or midface infection and is characterized by headache, fever, cranial nerve palsies, and periorbital edema. Ocular signs include chemosis, elevated intraocular pressure, ophthalmoplegia, and impaired visual acuity. Diagnosis is confirmed by imaging.

Rhino-orbital mucormycosis is caused by fungal infection and is usually seen in immunocompromised patients. Clinical findings include black eschar of the nasal mucosa or palate, sensory loss, and periocular pain. The periocular skin may also exhibit necrosis. Ocular signs include reduced pupillary response to light, impaired visual acuity, exophthalmos, and complete ophthalmoplegia.

Periorbital or orbital subperiosteal hematomas may resemble periorbital necrotizing fasciitis but usually follow traumatic injury, do not share the dramatic local and systemic deterioration that characterizes necrotizing fasciitis, and in most cases resolve spontaneously with conservative treatment.

Necrotizing fasciitis may present initially as a mild inflammation but exhibits rapid deterioration which must be recognized and treated promptly. Studies have shown that many cases of necrotizing fasciitis are misdiagnosed as non-necrotizing infections. In a large case series of generalized necrotizing fasciitis, approximately 15% of cases were correctly diagnosed as necrotizing fasciitis on admission. Nearly 60% of patients were misdiagnosed with cellulitis [13].

Clinically, three subtypes of necrotizing fasciitis have been identified. The fulminant variant progresses rapidly and may lead to toxic shock and multi-organ failure. The acute variant develops over days and typically affects large areas of the skin. The subacute type advances slowly over a period of weeks and involves localized areas [9]. The fulminant and acute types of necrotizing fasciitis are usually caused by β-hemolytic streptococci, whereas subacute cases are usually polymicrobial [9]. A rise in incidence of necrotizing fasciitis in the last decades is attributed to the increasing prevalence of group A streptococcal infection.

Orbital necrotizing fasciitis introduces a diagnostic challenge similar to that of necrotizing fasciitis of the trunk and extremities. In its early stages, it is occasionally characterized by mild symptoms that fail to imply the severity of the infection and its prognosis. Initially, periorbital necrotizing fasciitis may resemble a simple periorbital cellulitis or erysipelas, with pale red, tense, swollen skin. Patients may appear healthy overall, often with a mild to moderate fever, accompanied by exceptionally exaggerated tachycardia [9]. Severe and disproportionate pain develops at the site of infection and spreads as the process extends, while the involved skin may turn anesthetic due to nerve dysfunction. Crepitus can sometimes be palpated and may be seen as air in the affected soft tissue on plain radiographs or more advanced imaging. These signs are pathognomonic for necrotizing fasciitis; however, their absence does not exclude the diagnosis [1].

Tenderness is remarkable and usually involves areas beyond gross skin involvement. The disease may involve surrounding dermatomes, including V1-V3 [5], but cervical or mediastinal association is rare. As the disease process proceeds, patients feel systemically ill. Within 48 h the skin acquires a typical rose-violet color, which later can progress to fluid-filled bullae. The appearance of black patches is attributed to thrombosis of perforating vessels and indicates progression of the necrotic process. Evident gangrene is seen within 4–5 days, followed by underlying suppuration and sloughing of the skin within 8–10 days.

Laboratory findings include an extreme rise in leukocyte count, elevated C-reactive protein, and increase in the value of glucose, urea, and creatinine. Hypoalbuminemia, acidosis, and alteration in coagulation function can also be seen [4]. Systemic deterioration may manifest as a further elevation in body temperature, as well as signs of toxic shock, including hypotension, renal or multi-organ failure, reduced level of consciousness, and disseminated vascular coagulation. Toxic shock syndrome was reported in up to 30% of periocular NF cases and substantially increases the risk for mortality [2]. Ocular manifestations such as keratitis, uveitis, and chorioretinitis may be seen. Spread of the infection to the orbital region can cause ophthalmoplegia, proptosis, and impaired optic nerve function such as positive relative afferent pupillary defect (RAPD) . Necrosis of the medial upper lid was noted as a typical apparent sign affecting patients with orbital disease [5]. Orbital involvement is a predictor of either worse final visual acuity or, in the more severe cases, of the need of exenteration [5].

Periorbital necrotizing fasciitis behaves differently than in other body sites, due to specific anatomic characteristics of the region [2]. The eyelid skin is the thinnest in the body and lacks subcutaneous fat. Infection is noticeable in its early course, and evidence of necrosis and gangrene is more obvious. Therefore, the interval between the onset of symptoms and obvious deterioration is short [4, 12]. This should lead patients to seek medical treatment promptly and urge clinicians to act rapidly.

The rich vascularization of the eyelids contributes to eyelid resistance against the pathologic process which tends to spread along avascular planes. It also allows for better antibiotic access to the inflamed regions.

The orbicularis oculi muscle underneath the skin potentially comprises a vascularized barrier to the spreading infection, and the eyelid margins are often spared secondary to their extensive vascularization. Passage of the infectious process through the orbicularis muscle is possible but rare and leads to severe full-thickness eyelid or orbital tissue involvement. Dermal attachments at the nasojugal and malar folds further halt the spread of the infection. Resistant to nasal horizontal spreading, however, is poor, so bilateral involvement of the periorbital skin is not uncommon [4] (Fig. 9.1a, b).

The specific anatomic characteristics of the eyelids may possibly allow for a more conservative treatment in periocular necrotizing fasciitis. Sepsis incidence is lower than in necrotizing fasciitis affecting other body sites. Appropriate antibiotic treatment may inhibit disease progression, and mortality rates are significantly lower in periorbital necrotizing fasciitis than outside the eyelid region. The marginal areas adjacent to the necrotic tissue maintain an adequate blood supply, and the border between the affected and healthy tissue may be seen as autodemarcation. This unique phenomenon of autodemarcation in periocular necrotizing fasciitis enables delayed and less extensive debridement in select cases than that indicated in extraocular necrotizing fasciitis [10].

Early diagnosis, aggressive antibiotic treatment, and surgical debridement are the cornerstones to successful outcomes. A multidisciplinary approach, involving oculoplastic surgeons, plastic surgeons, dermatologists, ENT surgeons, and microbiologist, may be necessary.