Necrotizing fasciitis (periorbital)

Key points at a glance

Key points of this condition

• Necrotizing fasciitis (NF) is a life-threatening, severe infection that rapidly spreads through the superficial fascia and leads to skin necrosis.
• Periorbital necrotizing fasciitis is extremely rare, with an incidence of 0.24 per million people per year; reported mortality is 8–15% and vision loss is 13.8%.
• The causative organisms are broadly classified into type I (mixed infection) and type II (mainly group A streptococci), and mortality is higher in type II.
• Diagnosis is based mainly on clinical findings, with CT imaging and the LRINEC score (a risk assessment index for necrotizing soft tissue infection) used as aids.
• The basic treatment consists of three pillars: surgical debridement, antimicrobial therapy, and overall supportive care; only a very small number of periorbital necrotizing fasciitis cases have been successfully treated with medical therapy alone.
• Pyoderma gangrenosum and Sweet syndrome are representative conditions that can look clinically similar to necrotizing fasciitis and may be misdiagnosed.
• In pyoderma gangrenosum and Sweet syndrome, surgical debridement can worsen the lesions (pathergy), so the differential diagnosis directly affects treatment decisions.

1. What is necrotizing fasciitis

Necrotizing fasciitis is a destructive, rapidly progressing infection that involves the superficial fascia and leads to rapid skin necrosis. It is said that Hippocrates first recognized it in the 5th century BC. It is also called “flesh-eating bacteria infection,” “hospital gangrene,” “necrotizing erysipelas,” and “progressive bacterial synergistic gangrene.”

The most common sites are the abdomen, extremities, and perineum, and the periorbital area is rare because of the orbit’s rich blood supply and the firm tissue structure of the eyelids.

Epidemiology of general necrotizing fasciitis

• Incidence: 0.4 to 7.7 cases per 100,000 people¹⁾
• Annual new cases in the United States: about 10,000
• Mortality: 10–15% even with appropriate treatment¹⁾, 25–30% in general necrotizing fasciitis

Epidemiology of periorbital necrotizing fasciitis

• Incidence in the United Kingdom: 0.24 per 1,000,000 people per year (2-year prospective study by the UK Ophthalmic Surveillance Unit)
• Mortality: 8–15%
• Vision loss rate: 13.8%
• Average age at diagnosis: 50.18 years (reported by Lazzeri et al.)
• Sex difference: Some reports show it is more common in women (54%), while others report no difference between men and women

Q How rare is necrotizing fasciitis?

A

General necrotizing fasciitis has an incidence of 0.4 to 7.7 cases per 100,000 people and is not rare at all¹⁾. However, periorbital necrotizing fasciitis, which occurs around the eye socket, is extremely rare at 0.24 people per million per year. The rich blood supply of the orbit and the strong structure of the eyelids are thought to suppress its onset.

2. Main symptoms and clinical findings

Subjective symptoms

• Acute painful skin redness: It starts as a nonspecific erythematous rash.
• Swelling around the affected area: It tends to spread rapidly.
• Fever and severe pain: These become prominent when the infection spreads along the fascia.
• Rapid heart rate out of proportion to the fever: This reflects a systemic inflammatory response.

Clinical findings

Initial findings

Erysipelas/cellulitis-like: In the early stage, it is difficult to distinguish from preseptal cellulitis or erysipelas.

Skin erythema: Erythema with unclear borders and induration.

Edema: May extend beyond the area of skin erythema.

Progressive findings

Bullae formation: Within 48 hours, the eyelid skin turns purplish-red and forms fluid-filled bullae.

Black necrotic patches: Appear due to thrombosis of the dermal and subcutaneous perforating vessels.

Skin gangrene: Becomes apparent in 4-5 days and progresses to skin sloughing and gangrene in 8-10 days.

Early ocular lesions: Keratitis, uveitis, and chorioretinitis may occur.

Special features of periorbital necrotizing fasciitis

• The orbit is richly vascularized, and the eyelid skin is thin and lacks subcutaneous fat.
• Skin infection tends to become noticeable earlier.
• Necrosis of the thin eyelid progresses rapidly.
• The time from onset to treatment is usually short.
• The eyelid margin has blood supply from the eyelid margin arterial arcade and is often spared.

Q What helps distinguish necrotizing fasciitis from cellulitis?

A

According to the Infectious Diseases Society of America (IDSA) guidelines, the distinguishing features are: 1) severe pain that is out of proportion to the clinical findings, 2) poor response to initial antibiotics, 3) a woody, hard feel of the subcutaneous tissue, 4) systemic toxicity, 5) swelling and tenderness extending beyond the area of redness, 6) crepitus, 7) blistering lesions, and 8) skin necrosis or purpura. If these findings are present, necrotizing fasciitis should be strongly suspected and prompt treatment is needed.

3. Causes and risk factors

Microbiological classification

Type I: Mixed infection

Causative organisms: mixed infection with anaerobic bacteria, gram-negative rods, and enterococci.

Patient background: occurs mainly in immunocompromised patients.

Mortality rate: about 20%.

Type II: Streptococcal

Causative organisms: Group A streptococci (S. pyogenes) ± staphylococci.

Patient background: can also occur in people with normal immune function.

Mortality rate: 30–35%, higher than type I.

Common causative organisms include Streptococcus pyogenes, Staphylococcus aureus, and a mix of anaerobes and gram-negative bacteria¹⁾. Type III cases caused by gram-negative bacteria alone or by the genus Clostridium have also been reported³⁾. Cases caused by rare organisms such as Actinomyces europaeus and Clostridium innocuum have also been reported¹⁾. Aeromonas hydrophila lives in freshwater and saltwater environments and causes necrotizing fasciitis after water exposure²⁾.

Spread to the lower face and neck can lead to extension to the mediastinum, chest, and the area around the carotid sheath, increasing the risk of pulmonary complications and mortality.

Risk factors

• Common triggers: trauma and surgery. In about 27% of cases, no trigger can be identified (reported by Amrith et al.).
• Underlying conditions: older age, chronic kidney failure, peripheral vascular disease, diabetes, alcohol dependence, rheumatic disease, systemic malignancy, and immunosuppression.
• Medications: use of immunomodulatory drugs such as steroids and chemotherapy agents increases the incidence of necrotizing fasciitis.
• Other: obesity, after gastrointestinal surgery³⁾, and exposure to freshwater or saltwater environments²⁾.

Caution in patients with risk factors

When patients with diabetes or immunosuppression present with sudden pain and skin redness, rapid evaluation with necrotizing fasciitis in mind is necessary. Early diagnosis and treatment greatly affect the prognosis.

4. Diagnosis and testing methods

Clinical diagnosis (criteria of the Infectious Diseases Society of America)

Differential features between necrotizing fasciitis and cellulitis according to the IDSA guidelines (see also the main symptoms and clinical findings section):

1. Severe pain that does not match the clinical findings
2. Poor response to initial antibiotic treatment
3. Wooden-hard feel of the subcutaneous tissue (extending beyond the skin lesion)
4. Systemic toxicity
5. Edema and tenderness extending beyond the area of skin erythema
6. Crepitus (crackling sensation)
7. Bullous lesions
8. Skin necrosis and purpura

Definitive diagnosis: by deep tissue biopsy, Gram stain, and culture.

Imaging diagnosis

• CT (first-line): allows rapid identification of the initial infection site. It is excellent for detecting gas, fluid collections, and bullae, and provides anatomical information. It is essential for planning the surgical approach for periorbital necrotizing fasciitis.
• MRI: Useful for ruling out necrotizing fasciitis if there is no involvement of the fascia, subcutaneous tissue, or deep dermis. Sensitivity 90–100%, specificity 50–85%⁴⁾. Shows low signal on T1, high signal on T2, and contrast enhancement⁴⁾. However, pyoderma gangrenosum can also show high signal at the fascial level on MRI, so MRI alone has limits for diagnosis⁴⁾.

LRINEC score

Calculated using six items: C-reactive protein (CRP), white blood cell count, hemoglobin, sodium, creatinine, and blood glucose. A score of 6 or higher calls for further evaluation. However, high scores (>5) can also be seen in other musculoskeletal infections, so there are limits to using it alone for diagnosis¹⁾.

Q What is the LRINEC score?

A

The LRINEC score is a scoring system that uses six items—C-reactive protein, white blood cell count, hemoglobin, sodium, creatinine, and blood glucose—to assess the likelihood of necrotizing fasciitis. A score of 6 or higher calls for further evaluation¹⁾, but high scores can also occur in other musculoskeletal infections, so overall judgment with clinical findings is important.

Differential diagnosis

It is important to distinguish this from the following diseases.

Disease	Key points for differentiation	Treatment
Orbital cellulitis	No skin necrosis or gas formation. Often associated with sinus disease.	Responds to antibiotics
Erysipelas	Well-demarcated bright red raised plaque. No necrosis or deep spread	Responds to antibiotics
Rhino-cerebral-orbital mucormycosis	Immunocompromised patients and people with diabetes. Angioinvasive fungal infection	Antifungal drugs and surgery
Pyoderma gangrenosum	Sterile neutrophilic infiltration. Responds to steroids4)	Steroids
Sweet syndrome	Culture negative. Rapidly responds to steroids	Steroids

• Granulomatosis with polyangiitis: Chronic autoimmune vasculitis. c-ANCA positive. Necrotizing granulomas and palisading histiocytes are seen.
• Sarcoidosis: Slowly developing, non-infectious. Non-caseating granulomas are seen.
• Orbital tumor: Subacute proptosis and a mass lesion are characteristic.
• Warfarin-induced skin necrosis: 3 to 6 days after administration, purpura → hemorrhagic blisters → black eschar. Thrombotic and non-infectious.

Importance of differential diagnosis

Pyoderma gangrenosum and Sweet syndrome have clinical and imaging findings similar to necrotizing fasciitis. In these diseases, debridement can trigger pathergy (worsening of the lesion), so inappropriate surgical treatment can worsen the condition. Evaluation of pathogens by skin biopsy and culture is essential⁴⁾.

5. Standard treatment

Three pillars of treatment

1. Surgical debridement (mainstay): Serial debridement. There are only a very small number of cases of periorbital necrotizing fasciitis successfully treated with medical therapy alone.
2. Aggressive antibiotic therapy: Cover both aerobic bacteria (including methicillin-resistant Staphylococcus aureus (MRSA)) and anaerobic bacteria.
3. Systemic management: Fluid resuscitation and blood pressure support.

Antibiotic therapy

Recommended regimen (vancomycin + one of the following):

Concomitant drug	Notes
Piperacillin-tazobactam	Common first-line choice
Carbapenems	For severe cases and broad coverage
Ceftriaxone + metronidazole	Alternative option
Fluoroquinolone + metronidazole	Alternative option

• Add clindamycin: added to suppress streptococcal toxin and cytokine production.
• Adjusting the antibiotic based on culture and susceptibility test results is important¹⁾.
• Rare bacteria may show resistance even to drugs that are already known (reports of piperacillin/tazobactam resistance in Actinomyces europaeus and vancomycin resistance in C. innocuum)¹⁾.

Surgical approach to periorbital necrotizing fasciitis

• A CT-guided approach makes it possible to assess the extent of infection, check for the presence of gas, and obtain anatomical information.
• Preserving healthy tissue makes later reconstruction easier.
• Delay in debridement is strictly forbidden; it should be performed promptly once the diagnosis is confirmed.

Adjunctive therapy

• Intravenous immunoglobulin therapy (IVIG): Evidence for streptococcal toxic shock syndrome is limited. Lot-to-lot variation makes research difficult.
• Hyperbaric oxygen therapy: Reports suggest reduced mortality and improved tissue survival. It is expected to suppress exotoxin production, maintain leukocyte function, and kill anaerobic bacteria. However, debridement must not be delayed, and the risks of hyperbaric oxygen therapy itself must also be considered.
• Hypochlorous acid irrigation: Evidence supporting its effectiveness is increasing.
• Negative pressure wound therapy: Useful for making debridement easier and promoting granulation tissue formation. In the periorbital area, it carries a risk of increased intraocular pressure, worsening glaucoma, and central retinal vein occlusion, which can reduce vision. Some case reports have shown preserved vision and good cosmetic results.

Q Can necrotizing fasciitis be treated with antibiotics alone?

A

Only a very small number of cases of periorbital necrotizing fasciitis have been successfully treated with medical therapy alone, and surgical debridement is the mainstay of treatment. Antibiotic therapy is positioned as an adjunct to surgery, and the basic approach is to combine the three pillars (debridement, antibiotics, and systemic management).

6. Pathophysiology and detailed mechanisms of onset

Microorganisms enter the superficial fascia after trauma or surgery, leading to rapid spread of infection. The core disease process is infection of the superficial fascia → thrombosis of the dermal and subcutaneous perforating vessels → skin necrosis.

Large amounts of cytokines produced in association with infection (IL-1, IL-6, IL-8, interferon, and TNF-α) induce a procoagulant state, leading to disseminated intravascular coagulation (DIC) and microthrombus formation²⁾. As endothelial injury, platelet activation, increased tissue factor, and reduced fibrinolytic activity overlap, tissue ischemia rapidly progresses²⁾.

Around the orbit, the eyelid skin is thin and lacks subcutaneous fat, so infection tends to appear on the skin surface early. The eyelid margin is often preserved even as necrosis advances because it receives blood supply from the marginal arterial arcade.

Pathophysiologic comparison with Sweet syndrome

Sweet syndrome is associated with IL-1–activated cytokines and hypersensitivity to neutrophils, and is characterized by tissue destruction caused by neutrophilic infiltration rather than bacterial invasion. The three subtypes of Sweet syndrome are classified as classic (idiopathic), malignancy-associated (85% are hematologic cancers), and drug-induced.

In necrotizing fasciitis, surgical debridement is the main treatment, whereas in Sweet syndrome this procedure can trigger pathergy (worsening of the lesion). This fundamental difference supports the importance of making a definite distinction between the two diseases.

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7. Latest research and future outlook (reports at the research stage)

For patients: Please read this carefully

The following content is currently at the research stage or under clinical trial, and is not standard treatment available at general hospitals. It is reference information for specialists regarding future medical developments.

Recognition of necrotizing Sweet syndrome

Three immunocompromised patients misdiagnosed with necrotizing fasciitis were reported to have ‘necrotizing Sweet syndrome,’ which responded quickly to high-dose steroids. Eyelid necrotizing Sweet syndrome in patients with myelodysplastic syndrome/acute myeloid leukemia closely resembled necrotizing fasciitis clinically, but debridement triggered a pathergy reaction, and histology showed neutrophil infiltration with no microorganisms, so it improved with steroids. The importance of microbiological evaluation in intraoperative tissue biopsy was emphasized.

Limitations of MRI in differentiating pyoderma gangrenosum and necrotizing fasciitis

Park et al. (2022) reported a case of pyoderma gangrenosum that developed in a patient with acute myeloid leukemia⁴⁾. MRI showed high signal at the fascial level, and it was initially misdiagnosed as necrotizing fasciitis, but broad-spectrum antibiotics were ineffective. Skin biopsy showed neutrophil infiltration, vascular changes (fibrinoid necrosis), and no microorganisms, confirming pyoderma gangrenosum. It resolved completely with intravenous methylprednisolone. It showed that differentiation by MRI alone is insufficient, and skin biopsy is essential⁴⁾.

Necrotizing fasciitis caused by rare bacteria

Avery et al. (2025) reported a case of necrotizing fasciitis of the thigh caused by Actinomyces europaeus and Clostridium innocuum¹⁾. Empiric treatment was started with vancomycin + piperacillin/tazobactam + clindamycin, but based on culture results it was changed to meropenem + linezolid. Multiple extensive debridements were performed, but the patient died 30 days later. The importance of rapid species identification by MALDI-TOF mass spectrometry was noted¹⁾.

Q Why are Sweet syndrome and necrotizing fasciitis easily confused?

A

The clinical picture of both conditions is very similar, with acute skin necrosis, fever, and pain. Sweet syndrome can also show spread to the fascial level on MRI⁴⁾. The key distinction is that surgical debridement is effective in necrotizing fasciitis, whereas in Sweet syndrome debridement can trigger pathergy (worsening of the lesion), and the condition responds quickly to steroids. Skin biopsy and culture to assess for pathogens are essential for a reliable differential diagnosis.

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8. References

1. Avery L, Kufel J, Rawlings R. Treatment of Actinomyces europaeus and Clostridium innocuum necrotizing fasciitis: Case report and literature review. American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists. 2025;82(23):e946-e955. doi:10.1093/ajhp/zxaf190. PMID:40701608; PMCID:PMC12640710.
2. Zhen Zhang, Xiao-Dan Zhao, Guanglin Wang, Fuguo Huang. Aeromonas hydrophila-related fulminant necrotizing fasciitis and arterial embolization after plaster placement in Gustilo I distal radius fracture: a case report and literature review. BMC Musculoskelet Disord. 2025;26(1). doi:10.1186/s12891-025-08934-z.
3. Sablone S, Lagouvardou E, Cazzato G, Carravetta F, Maselli R, Merlanti F, et al. Necrotizing Fasciitis of the Thigh as Unusual Colonoscopic Polypectomy Complication: Review of the Literature with Case Presentation. Medicina (Kaunas). 2022;58(1):131. doi:10.3390/medicina58010131. PMID:35056439; PMCID:PMC8780250.
4. Park S, Shin H, Lee DH, Koh EH, Lee JH, Lee GW.. Pyoderma Gangrenosum Mimicking Necrotizing Fasciitis on Magnetic Resonance Imaging: A Case Report and Literature Review. Am J Case Rep. 2022;23:e931734. doi:10.12659/ajcr.931734. PMID:36045564; PMCID:PMC9444165.