Accepted Manuscript Periocular Necrotizing Fasciitis in an Infant Alan D. Proia, M.D., Ph.D. PII:
S0039-6257(16)30263-6
DOI:
10.1016/j.survophthal.2017.03.002
Reference:
SOP 6709
To appear in:
Survey of Ophthalmology
Received Date: 29 November 2016 Revised Date:
27 February 2017
Accepted Date: 3 March 2017
Please cite this article as: Proia AD, Periocular Necrotizing Fasciitis in an Infant, Survey of Ophthalmology (2017), doi: 10.1016/j.survophthal.2017.03.002. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT
Clinical Pathologic Reviews
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Periocular Necrotizing Fasciitis in an Infant
Alan D. Proia, M.D., Ph.D. Duke University Medical Center
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Department of Pathology - DUMC 3712
Telephone: (919)684-2482 Facsimile: (919)684-2625
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E-Mail: [email protected]
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Durham, N.C. 27710
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ABSTRACT
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A 12-month-old boy developed periocular necrotizing fasciitis with swelling of both eyes and redness and a discharge from the left eye approximately 36 hours after blunt trauma. Computed tomography revealed pre-septal and soft tissue edema on the left side, but no signs of orbital
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involvement, orbital fractures, or drainable abscess in the anterior left lower eyelid. The
inflammatory signs worsened over the next day, and there was purulent discharge from the left
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lower eyelid and an abscess and necrosis of the lower eyelid skin. He did well following surgical debridement and treatment with intravenous antibiotics. His course highlights the difficulty in diagnosing necrotizing fasciitis and the necessity for prompt surgical debridement and empirical
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broad-spectrum antibiotic therapy.
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Key Words: Periocular; eyelid; fascia; necrotizing fasciitis; cellulitis; Streptococcus pyogenes
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1. Introduction Necrotizing fasciitis is a rare, rapidly progressing bacterial infection that originates in the
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fascia and involves muscles and subcutaneous fat with later necrosis of the overlying skin.11,20,22,44 The clinical diagnosis of necrotizing fasciitis is difficult,11,20,22,43,44 and there is a high mortality despite treatment.20 Herein, I present the youngest infant reported with periocular necrotizing
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fasciitis and review fascia, necrotizing fasciitis in adults and children, and periocular necrotizing
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fasciitis.
2. Clinical presentation
A 12-month-old boy was evaluated for swelling of both eyes and redness and a discharge from the left eye approximately 36 hours after blunt periocular trauma. The parents gave
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discrepant histories with one stating that the boy fell out of his crib and the other saying the child was struck with a toy by his sister. Physical examination upon admission noted 1+ upper and lower eyelid edema on the right side with erythema and no warmth. There was 2+ left upper
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eyelid edema with ecchymosis; 3+ left lower eyelid and left facial edema, erythema, and induration, but no warmth; and an area of abraded necrotic skin close to the lower eyelid margin
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(Fig. 1A). The conjunctiva on the right side was unremarkable, while on the left side there was 2+ conjunctival chemosis with minimal mucopurulent discharge from 6:00 to 9:00 o’clock. Both corneas, anterior chambers, irides, lenses, and vitreous compartments were unremarkable, as was the fundus examination. Computed tomography revealed pre-septal and soft tissue edema on the left side but no signs of orbital involvement, orbital fractures, or drainable abscess in the anterior left lower eyelid (Fig. 2A-C). The clinical diagnosis was preseptal cellulitis, and he was treated
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with topical bacitracin ointment and intravenous infusion of piperacillin-tazobactam (Zosyn®) and
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vancomycin. Culture of the pus grew 4+ Streptococcus pyogenes (group A beta-hemolytic streptococcus).
The inflammatory signs worsened over the next day, and there was purulent discharge from the left lower eyelid with an abscess and necrosis of the lower eyelid skin (Fig 1B). The
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child underwent debridement of the skin and subcutaneous tissue. During surgery, a 10 x 20 mm
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abscess cavity was found in the left lower eyelid with a necrotic break in the tissue at the left lower eyelid lash line. The tissue surrounding the abscess was friable, necrotic, and did not bleed. The necrotic tissue was removed along with a rim of viable bleeding tissue. The surgical debridement extended to the superior malar region, the lateral canthus, and the medial canthus. Necrotic tissue and purulence extended into the anterior inferior orbit. This tissue was debrided,
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and a Penrose drain was fenestrated and inserted into the inferior left orbit. A lid crease incision into the left upper eyelid did not disclose any evidence of infection. The child did well following surgery and treatment with intravenous antibiotics. He was discharged from the hospital three
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weeks after surgery.
The child’s medical history was noteworthy only for critical pulmonary valve stenosis
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diagnosed at birth and treated with balloon valvuloplasty within hours of birth.
3. Pathology
Histological sections contained skeletal muscle (Fig. 3A) and connective tissue (Fig. 3B) with an infiltrate of predominantly neutrophils and a lesser number of macrophages accompanied
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by extensive necrosis and areas with numerous bacterial cocci (Fig 3C). Rare vessels contained
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fibrin thrombi (Fig 3D), while others were inflamed and partially necrotic.
4. Discussion
4A. What is fascia? Before considering necrotizing fasciitis, it is worth considering what
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is meant by fascia. While this seems like a simple task, the meaning of the term “fascia” is
controversial and in flux as a result of the potential clinical relevance of fascial dysfunction in
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disorders such as chronic pain syndromes and pelvic floor laxity.15,19,34,36 The 1998 edition of Terminologia Anatomica uses “fascia” to indicate “…sheaths, sheets or other dissectible connective tissue aggregations”34 including “investments of viscera and dissectible structures related to them…”.34 The 39th edition of Gray’s Anatomy, published in 2005, uses “fascia” only
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for deep fascia and notes “Fascia is a term so vague in use that it signifies little more than assemblages of connective tissue large enough to be visible to the unaided eye. The practice of attaching a name to any aggregation that is large enough to be dissected is of dubious value.”36
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In an attempt to rectify this confusion, these recent proposals have been made: 1. Stecco and colleagues36 propose dividing fascia into superficial fascia, which divides
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subcutaneous tissue into two layers, and deep fascia, which envelops all the muscles of
the body. Superficial fascia, according to this scheme, is thicker in the trunk than the extremities, may contain muscle fibers, and includes veins with thin ligaments connecting their adventitia to the fascia, as well as the hypodermal plexus of arteries and veins. Deep fascia is subdivided into aponeurotic fascia and epimysial fascia. Epimysial fascia connects tightly to underlying muscle by multiple fibrous septa.
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and innervation to classify fascia functionally into four categories: i) linking, ii) fascicular, iii) compression, and iv) separating fascia. Linking fascia is subdivided into dynamic (related to movement and joint stability) and passive (“acted on by other extramuscular tissues to maintain continuity throughout the body or form tunnels and
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sheaths”). Fascicular fascia forms “adaptable tunnels which bundle vessels as well as
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fascicles within muscle, tendon, bone and nerves”. Compression fascia “ensheath whole limbs to create a stocking effect”, and they are important for locomotion and venous return. Separating fascia “divides the body in visible sheets and layers of varying fibers allowing it to take up forces and friction in all directions” and is important for allowing efficient sliding of tissues over one another.
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Of these two schemes, I prefer that of Stecco and colleagues36 owing to its simplicity. The Kumka and Bonar classification19 is probably the more correct anatomically and is more applicable to the complex anatomy of the orbit and ocular adnexa.
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Orbital fascia are an intricate array of collagenous septa containing varying amounts of smooth muscle cells, nerves, and blood vessels, with attachments to extraocular muscles and the
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periosteum of the orbital bones.17,18 The spatial architecture of the fascia varies in different regions of the orbit.17 Orbital fascia serve as a flexible supporting system for normal eye movement,17,18 are inflamed in Graves disease,18 and help to contain orbital hemorrhage in young patients.18 Intraorbital fascia blend into the orbital septum and then extend into fascial septa of the eyelids.18,28 Scarring of intraorbital fascia may influence eyelid lengthening procedures due to
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and eyebrow motility.28 4B. Necrotizing fasciitis.
Clinical features. Necrotizing fasciitis (NF), “flesh-eating disease” in the lay press,9,22 is a rare, rapidly progressing infection that starts in the fascia and involves muscles and
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subcutaneous fat, with later necrosis of the overlying skin.11,20,22,44 NF is conventionally classified into type 1 and 2 disease, with type 1 being polymicrobial with at least one anaerobic species
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together with one or more facultative anaerobic bacteria.20 Type 2 NF is monomicrobial, with invasive group A Streptococcus pyogenes being the most common pathogen.20,37 Type 1 NF accounts for 55% to 75% of all cases of necrotizing fasciitis, and it is most frequent on the trunk, abdomen, and perineum.20 Type 2 NF most commonly involves the head/neck or the extremities20
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and is associated with minor cutaneous injuries20 or nonpenetrating blunt trauma29 in otherwise healthy, immunocompetent people.20
NF is predominantly an adult disease, with a markedly increasing incidence above the age
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of 60 years.25 In 1995, the incidence of group A streptococcal NF was 0.40 cases per 100,000 population in the province of Ontario, Canada.38 In a more recent study from Denmark including
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the years 2003-2004, the overall annual incidence of invasive group A streptococcal infections was 2.6 cases per 100,000 individuals, but increased to approximately 4-5/100,000 in the 60-69 year age group and 11-12/1000,000 above age 80.25 In a study of 163 patients with NF from Loma Linda, California, the average age was 43 years. There were 91 men and 72 women, and predisposing factors included diabetes mellitus and intravenous drug use. Mortality was 28%.5 Factors that were significantly correlated with death were age < 1 years or age >60 years,
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intravenous drug use, the comorbid conditions of cancer, renal insufficiency/failure, peripheral vascular disease, and congestive heart failure, positive blood culture, trunk or perineal
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involvement, and delay in treatment.5 The mortality rate for NF has remained almost constant at 25% to 30% for the past century.20
Diagnosis. The clinical diagnosis of NF is notoriously difficult,11,20,22,43,44 especially early
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in the disease when it is frequently diagnosed as cellulitis or abscess.20 Clinical features early in the disease include tenderness to palpation, erythema, swelling, and warm skin.43 Later, blisters or
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bullae form, followed by crepitus, skin anesthesia, and skin necrosis with dusky discoloration.43 Clinical clues to early diagnosis are pain out of proportion to the physical findings, failure to respond to broad-spectrum antibiotics, skin bullae, and soft tissue gas on x-ray.11,31 Operative findings include grayish necrotic fascia, lack of resistance of superficial fascia to blunt dissection,
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lack of bleeding of fascia during dissection, and foul-smelling pus.44 Frozen-section biopsy is particularly useful for early recognition of NF.35 Cultures should be obtained either before or during surgery to guide antibiotic therapy. Histochemical stains for microorganisms should be
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reserved for cases in which cultures were not obtained. Pathology. The histopathology of NF varies depending on how long the disease has been
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present.3,6,35,42 Stamenkovic and Lew35 used these criteria for diagnosing NF: “(1) necrosis of superficial fascia, (2) polymorphonuclear infiltration of the deep dermis and fascia, (3) fibrinous thrombi of arteries and veins passing through the fascia, (4) angiitis with fibrinoid necrosis of arterial and venous walls, (5) the presence of microorganisms within the destroyed fascia and dermis in a tissue specimen with Gram stain, and (6) an absence of muscle involvement.” Thrombi are more frequent early in the course of streptococcal necrotizing fasciitis3 and
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NF.6
Treatment. The mainstays of treatment of NF are surgical debridement until brisk
bleeding occurs from adjacent tissue and empirical broad-spectrum antibiotic therapy.20 Antibiotic
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sensitivities from cultures obtained before or during surgery should be used to refine therapy. Pediatric Necrotizing fasciitis. Only a few series describing pediatric NF are
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available.4,10,31 Factors predisposing children to NF are varicella (chickenpox), surgery, minor trauma, and malnutrition.4,10,31 In neonates, the use of scalp monitors, scalp lacerations, omphalitis, and circumcision are associated with NF.31 Clinical signs and symptoms, treatment, histopathology, diagnosis, and prognosis appear to be similar to adult NF, though the small
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number of pediatric cases makes comparison difficult.
4C. Periocular necrotizing fasciitis. Periocular NF is even rarer than NF elsewhere in the body, as evidenced by most publications being individual case reports2,8,12-14,16,23,24,30,39,40 or small
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series including from 3 to 11 patients.7,26,27,33,41 Most recently, however, a multicenter case series from three Australian and two United Kingdom hospitals included 29 patients.32 In addition, there
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are two recent reviews of periocular (periorbital) NF encompassing 941 and 10421 patients. The review by Lazzeri and coworkers,21 based on 104 patients, noted these findings: 1. Age range: 17 months to 93 years; median age = 45 years; average age = 50 years.
2. Gender distribution: 55% men, 45% women. 3. Preceding injury or infection: none (28%); eyelid laceration, penetrating injury, or abrasion (22%); blunt trauma (17%); blepharoplasty, dacryocystorhinostomy, biopsy,
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or self-puncture or excision (12%); upper respiratory infection or carbuncle (5%); and
eyelid abscess, rhinoplasty, parotiditis, and dacryocystis.
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insect bite (5%). Other causes of periocular NF were human bites, tooth extraction,
4. Predisposing conditions: none (50%); alcoholism (19%); diabetes mellitus (8%); rheumatological disease (5%); and malignancy (4%).
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5. Bacteriology: beta-hemolytic streptococci (50%, with Streptococcus pyogenes in 81%
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of these); mixed beta-hemolytic streptococci and Staphylococcus aureus (18%); Staphylococcus aureus (5%); Pseudomonas aeruginosa (3%); and polymicrobial (19%).
6. Outcome: survival = 86%, with 7 undergoing orbital exenteration. Only one of 29 patients (3%) died in the more recent multicenter series reported by Rajak et al.32
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Vision loss and impairment were not tabulated by Lazzeri and coworkers.21 Amrith, Pai, and Ling in their review of 94 patients with periocular NF reported that vision was not affected in 71% of patients, and was “impaired” in 3%. Blindness occurred in 14%, and visual outcome was
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not reported in 12%.1 Rajak et al. reported visual loss in 14% of patients.32 Five of the seven patients reported by Elner et al. developed severe loss of vision (no light perception in 4 eyes and
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count fingers in 1 eye), though all of these patients had bilateral periocular NF.7
5. Conclusion
The clinical diagnosis of NF is extremely difficult, especially early in the disease when it is frequently diagnosed as cellulitis or abscess. Clinical clues to early diagnosis are pain out of proportion to the physical findings, failure to respond to broad-spectrum antibiotics, skin bullae,
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and soft tissue gas on x-ray. This child illustrates the rapidity with which NF progresses and
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typical histopathological features of the disease. Prompt surgical debridement and empirical broad-spectrum antibiotic therapy are the mainstays for treating NF.
6. Method of literature search
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Literature search was completed using Google Scholar with the following search terms and
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combinations: “fascia + review”, “necrotizing fasciitis + review”, “necrotizing fasciitis + periocular”, “necrotizing fasciitis + eye”, “necrotizing fasciitis + children”, “necrotizing fasciitis + periocular + children”, “periocular necrotizing fasciitis”, and “periocular necrotizing fasciitis +
7. Abbreviations NF = necrotizing fasciitis
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8. Acknowledgment
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children”. The Google Scholar searches did not include any language or date restrictions.
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Jason A. Liss, M.D. provided figure 1B and Ms. Susan Reeves prepared the composite figures.
9. Funding/Support
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
10. Financial Disclosure
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None to report
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Figure Legends
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Figure 1. A. Upon admission there was mild (1+) upper and lower eyelid edema on the right side with erythema and no warmth. There was moderate (2+) left upper eyelid edema with
ecchymosis; severe (3+) left lower eyelid and left facial edema, erythema, and induration but no
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warmth; and an area of abraded necrotic skin close to the lower eyelid margin. B. The
inflammatory signs worsened over the next day, and there was purulent discharge from the left
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lower eyelid and an abscess and necrosis of the lower eyelid skin.
Figure 2. Coronal (A), saggital (B), and axial (C) computed tomography revealed pre-septal and soft tissue edema (arrowheads) on the left side but no signs of orbital involvement, no orbital
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fractures, and no drainable abscess in the anterior left lower eyelid.
Figure 3. Skeletal muscle (A; hematoxylin and eosin, bar = 50 µm) and fascial connective tissue
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(B; hematoxylin and eosin, bar = 50 µm) were infiltrated by neutrophils and macrophages, accompanied by extensive necrosis and areas with numerous bacterial cocci causing a stippled
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appearance in the hematoxylin and eosin stained sections (C; hematoxylin and eosin, bar = 10 µm). Rare vessels (arrow) contained fibrin thrombi (D; hematoxylin and eosin, bar = 50 µm).
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ACCEPTED MANUSCRIPT
S0039-6257(16)30263-6
DOI:
10.1016/j.survophthal.2017.03.002
Reference:
SOP 6709
To appear in:
Survey of Ophthalmology
Received Date: 29 November 2016 Revised Date:
27 February 2017
Accepted Date: 3 March 2017
Please cite this article as: Proia AD, Periocular Necrotizing Fasciitis in an Infant, Survey of Ophthalmology (2017), doi: 10.1016/j.survophthal.2017.03.002. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Clinical Pathologic Reviews
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Periocular Necrotizing Fasciitis in an Infant
Alan D. Proia, M.D., Ph.D. Duke University Medical Center
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Department of Pathology - DUMC 3712
Telephone: (919)684-2482 Facsimile: (919)684-2625
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E-Mail: [email protected]
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Durham, N.C. 27710
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ABSTRACT
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A 12-month-old boy developed periocular necrotizing fasciitis with swelling of both eyes and redness and a discharge from the left eye approximately 36 hours after blunt trauma. Computed tomography revealed pre-septal and soft tissue edema on the left side, but no signs of orbital
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involvement, orbital fractures, or drainable abscess in the anterior left lower eyelid. The
inflammatory signs worsened over the next day, and there was purulent discharge from the left
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lower eyelid and an abscess and necrosis of the lower eyelid skin. He did well following surgical debridement and treatment with intravenous antibiotics. His course highlights the difficulty in diagnosing necrotizing fasciitis and the necessity for prompt surgical debridement and empirical
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broad-spectrum antibiotic therapy.
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Key Words: Periocular; eyelid; fascia; necrotizing fasciitis; cellulitis; Streptococcus pyogenes
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1. Introduction Necrotizing fasciitis is a rare, rapidly progressing bacterial infection that originates in the
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fascia and involves muscles and subcutaneous fat with later necrosis of the overlying skin.11,20,22,44 The clinical diagnosis of necrotizing fasciitis is difficult,11,20,22,43,44 and there is a high mortality despite treatment.20 Herein, I present the youngest infant reported with periocular necrotizing
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fasciitis and review fascia, necrotizing fasciitis in adults and children, and periocular necrotizing
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fasciitis.
2. Clinical presentation
A 12-month-old boy was evaluated for swelling of both eyes and redness and a discharge from the left eye approximately 36 hours after blunt periocular trauma. The parents gave
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discrepant histories with one stating that the boy fell out of his crib and the other saying the child was struck with a toy by his sister. Physical examination upon admission noted 1+ upper and lower eyelid edema on the right side with erythema and no warmth. There was 2+ left upper
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eyelid edema with ecchymosis; 3+ left lower eyelid and left facial edema, erythema, and induration, but no warmth; and an area of abraded necrotic skin close to the lower eyelid margin
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(Fig. 1A). The conjunctiva on the right side was unremarkable, while on the left side there was 2+ conjunctival chemosis with minimal mucopurulent discharge from 6:00 to 9:00 o’clock. Both corneas, anterior chambers, irides, lenses, and vitreous compartments were unremarkable, as was the fundus examination. Computed tomography revealed pre-septal and soft tissue edema on the left side but no signs of orbital involvement, orbital fractures, or drainable abscess in the anterior left lower eyelid (Fig. 2A-C). The clinical diagnosis was preseptal cellulitis, and he was treated
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with topical bacitracin ointment and intravenous infusion of piperacillin-tazobactam (Zosyn®) and
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vancomycin. Culture of the pus grew 4+ Streptococcus pyogenes (group A beta-hemolytic streptococcus).
The inflammatory signs worsened over the next day, and there was purulent discharge from the left lower eyelid with an abscess and necrosis of the lower eyelid skin (Fig 1B). The
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child underwent debridement of the skin and subcutaneous tissue. During surgery, a 10 x 20 mm
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abscess cavity was found in the left lower eyelid with a necrotic break in the tissue at the left lower eyelid lash line. The tissue surrounding the abscess was friable, necrotic, and did not bleed. The necrotic tissue was removed along with a rim of viable bleeding tissue. The surgical debridement extended to the superior malar region, the lateral canthus, and the medial canthus. Necrotic tissue and purulence extended into the anterior inferior orbit. This tissue was debrided,
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and a Penrose drain was fenestrated and inserted into the inferior left orbit. A lid crease incision into the left upper eyelid did not disclose any evidence of infection. The child did well following surgery and treatment with intravenous antibiotics. He was discharged from the hospital three
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weeks after surgery.
The child’s medical history was noteworthy only for critical pulmonary valve stenosis
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diagnosed at birth and treated with balloon valvuloplasty within hours of birth.
3. Pathology
Histological sections contained skeletal muscle (Fig. 3A) and connective tissue (Fig. 3B) with an infiltrate of predominantly neutrophils and a lesser number of macrophages accompanied
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by extensive necrosis and areas with numerous bacterial cocci (Fig 3C). Rare vessels contained
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fibrin thrombi (Fig 3D), while others were inflamed and partially necrotic.
4. Discussion
4A. What is fascia? Before considering necrotizing fasciitis, it is worth considering what
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is meant by fascia. While this seems like a simple task, the meaning of the term “fascia” is
controversial and in flux as a result of the potential clinical relevance of fascial dysfunction in
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disorders such as chronic pain syndromes and pelvic floor laxity.15,19,34,36 The 1998 edition of Terminologia Anatomica uses “fascia” to indicate “…sheaths, sheets or other dissectible connective tissue aggregations”34 including “investments of viscera and dissectible structures related to them…”.34 The 39th edition of Gray’s Anatomy, published in 2005, uses “fascia” only
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for deep fascia and notes “Fascia is a term so vague in use that it signifies little more than assemblages of connective tissue large enough to be visible to the unaided eye. The practice of attaching a name to any aggregation that is large enough to be dissected is of dubious value.”36
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In an attempt to rectify this confusion, these recent proposals have been made: 1. Stecco and colleagues36 propose dividing fascia into superficial fascia, which divides
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subcutaneous tissue into two layers, and deep fascia, which envelops all the muscles of
the body. Superficial fascia, according to this scheme, is thicker in the trunk than the extremities, may contain muscle fibers, and includes veins with thin ligaments connecting their adventitia to the fascia, as well as the hypodermal plexus of arteries and veins. Deep fascia is subdivided into aponeurotic fascia and epimysial fascia. Epimysial fascia connects tightly to underlying muscle by multiple fibrous septa.
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and innervation to classify fascia functionally into four categories: i) linking, ii) fascicular, iii) compression, and iv) separating fascia. Linking fascia is subdivided into dynamic (related to movement and joint stability) and passive (“acted on by other extramuscular tissues to maintain continuity throughout the body or form tunnels and
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sheaths”). Fascicular fascia forms “adaptable tunnels which bundle vessels as well as
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fascicles within muscle, tendon, bone and nerves”. Compression fascia “ensheath whole limbs to create a stocking effect”, and they are important for locomotion and venous return. Separating fascia “divides the body in visible sheets and layers of varying fibers allowing it to take up forces and friction in all directions” and is important for allowing efficient sliding of tissues over one another.
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Of these two schemes, I prefer that of Stecco and colleagues36 owing to its simplicity. The Kumka and Bonar classification19 is probably the more correct anatomically and is more applicable to the complex anatomy of the orbit and ocular adnexa.
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Orbital fascia are an intricate array of collagenous septa containing varying amounts of smooth muscle cells, nerves, and blood vessels, with attachments to extraocular muscles and the
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periosteum of the orbital bones.17,18 The spatial architecture of the fascia varies in different regions of the orbit.17 Orbital fascia serve as a flexible supporting system for normal eye movement,17,18 are inflamed in Graves disease,18 and help to contain orbital hemorrhage in young patients.18 Intraorbital fascia blend into the orbital septum and then extend into fascial septa of the eyelids.18,28 Scarring of intraorbital fascia may influence eyelid lengthening procedures due to
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and eyebrow motility.28 4B. Necrotizing fasciitis.
Clinical features. Necrotizing fasciitis (NF), “flesh-eating disease” in the lay press,9,22 is a rare, rapidly progressing infection that starts in the fascia and involves muscles and
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subcutaneous fat, with later necrosis of the overlying skin.11,20,22,44 NF is conventionally classified into type 1 and 2 disease, with type 1 being polymicrobial with at least one anaerobic species
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together with one or more facultative anaerobic bacteria.20 Type 2 NF is monomicrobial, with invasive group A Streptococcus pyogenes being the most common pathogen.20,37 Type 1 NF accounts for 55% to 75% of all cases of necrotizing fasciitis, and it is most frequent on the trunk, abdomen, and perineum.20 Type 2 NF most commonly involves the head/neck or the extremities20
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and is associated with minor cutaneous injuries20 or nonpenetrating blunt trauma29 in otherwise healthy, immunocompetent people.20
NF is predominantly an adult disease, with a markedly increasing incidence above the age
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of 60 years.25 In 1995, the incidence of group A streptococcal NF was 0.40 cases per 100,000 population in the province of Ontario, Canada.38 In a more recent study from Denmark including
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the years 2003-2004, the overall annual incidence of invasive group A streptococcal infections was 2.6 cases per 100,000 individuals, but increased to approximately 4-5/100,000 in the 60-69 year age group and 11-12/1000,000 above age 80.25 In a study of 163 patients with NF from Loma Linda, California, the average age was 43 years. There were 91 men and 72 women, and predisposing factors included diabetes mellitus and intravenous drug use. Mortality was 28%.5 Factors that were significantly correlated with death were age < 1 years or age >60 years,
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intravenous drug use, the comorbid conditions of cancer, renal insufficiency/failure, peripheral vascular disease, and congestive heart failure, positive blood culture, trunk or perineal
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involvement, and delay in treatment.5 The mortality rate for NF has remained almost constant at 25% to 30% for the past century.20
Diagnosis. The clinical diagnosis of NF is notoriously difficult,11,20,22,43,44 especially early
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in the disease when it is frequently diagnosed as cellulitis or abscess.20 Clinical features early in the disease include tenderness to palpation, erythema, swelling, and warm skin.43 Later, blisters or
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bullae form, followed by crepitus, skin anesthesia, and skin necrosis with dusky discoloration.43 Clinical clues to early diagnosis are pain out of proportion to the physical findings, failure to respond to broad-spectrum antibiotics, skin bullae, and soft tissue gas on x-ray.11,31 Operative findings include grayish necrotic fascia, lack of resistance of superficial fascia to blunt dissection,
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lack of bleeding of fascia during dissection, and foul-smelling pus.44 Frozen-section biopsy is particularly useful for early recognition of NF.35 Cultures should be obtained either before or during surgery to guide antibiotic therapy. Histochemical stains for microorganisms should be
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reserved for cases in which cultures were not obtained. Pathology. The histopathology of NF varies depending on how long the disease has been
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present.3,6,35,42 Stamenkovic and Lew35 used these criteria for diagnosing NF: “(1) necrosis of superficial fascia, (2) polymorphonuclear infiltration of the deep dermis and fascia, (3) fibrinous thrombi of arteries and veins passing through the fascia, (4) angiitis with fibrinoid necrosis of arterial and venous walls, (5) the presence of microorganisms within the destroyed fascia and dermis in a tissue specimen with Gram stain, and (6) an absence of muscle involvement.” Thrombi are more frequent early in the course of streptococcal necrotizing fasciitis3 and
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NF.6
Treatment. The mainstays of treatment of NF are surgical debridement until brisk
bleeding occurs from adjacent tissue and empirical broad-spectrum antibiotic therapy.20 Antibiotic
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sensitivities from cultures obtained before or during surgery should be used to refine therapy. Pediatric Necrotizing fasciitis. Only a few series describing pediatric NF are
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available.4,10,31 Factors predisposing children to NF are varicella (chickenpox), surgery, minor trauma, and malnutrition.4,10,31 In neonates, the use of scalp monitors, scalp lacerations, omphalitis, and circumcision are associated with NF.31 Clinical signs and symptoms, treatment, histopathology, diagnosis, and prognosis appear to be similar to adult NF, though the small
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number of pediatric cases makes comparison difficult.
4C. Periocular necrotizing fasciitis. Periocular NF is even rarer than NF elsewhere in the body, as evidenced by most publications being individual case reports2,8,12-14,16,23,24,30,39,40 or small
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series including from 3 to 11 patients.7,26,27,33,41 Most recently, however, a multicenter case series from three Australian and two United Kingdom hospitals included 29 patients.32 In addition, there
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are two recent reviews of periocular (periorbital) NF encompassing 941 and 10421 patients. The review by Lazzeri and coworkers,21 based on 104 patients, noted these findings: 1. Age range: 17 months to 93 years; median age = 45 years; average age = 50 years.
2. Gender distribution: 55% men, 45% women. 3. Preceding injury or infection: none (28%); eyelid laceration, penetrating injury, or abrasion (22%); blunt trauma (17%); blepharoplasty, dacryocystorhinostomy, biopsy,
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or self-puncture or excision (12%); upper respiratory infection or carbuncle (5%); and
eyelid abscess, rhinoplasty, parotiditis, and dacryocystis.
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insect bite (5%). Other causes of periocular NF were human bites, tooth extraction,
4. Predisposing conditions: none (50%); alcoholism (19%); diabetes mellitus (8%); rheumatological disease (5%); and malignancy (4%).
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5. Bacteriology: beta-hemolytic streptococci (50%, with Streptococcus pyogenes in 81%
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of these); mixed beta-hemolytic streptococci and Staphylococcus aureus (18%); Staphylococcus aureus (5%); Pseudomonas aeruginosa (3%); and polymicrobial (19%).
6. Outcome: survival = 86%, with 7 undergoing orbital exenteration. Only one of 29 patients (3%) died in the more recent multicenter series reported by Rajak et al.32
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Vision loss and impairment were not tabulated by Lazzeri and coworkers.21 Amrith, Pai, and Ling in their review of 94 patients with periocular NF reported that vision was not affected in 71% of patients, and was “impaired” in 3%. Blindness occurred in 14%, and visual outcome was
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not reported in 12%.1 Rajak et al. reported visual loss in 14% of patients.32 Five of the seven patients reported by Elner et al. developed severe loss of vision (no light perception in 4 eyes and
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count fingers in 1 eye), though all of these patients had bilateral periocular NF.7
5. Conclusion
The clinical diagnosis of NF is extremely difficult, especially early in the disease when it is frequently diagnosed as cellulitis or abscess. Clinical clues to early diagnosis are pain out of proportion to the physical findings, failure to respond to broad-spectrum antibiotics, skin bullae,
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and soft tissue gas on x-ray. This child illustrates the rapidity with which NF progresses and
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typical histopathological features of the disease. Prompt surgical debridement and empirical broad-spectrum antibiotic therapy are the mainstays for treating NF.
6. Method of literature search
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Literature search was completed using Google Scholar with the following search terms and
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combinations: “fascia + review”, “necrotizing fasciitis + review”, “necrotizing fasciitis + periocular”, “necrotizing fasciitis + eye”, “necrotizing fasciitis + children”, “necrotizing fasciitis + periocular + children”, “periocular necrotizing fasciitis”, and “periocular necrotizing fasciitis +
7. Abbreviations NF = necrotizing fasciitis
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8. Acknowledgment
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children”. The Google Scholar searches did not include any language or date restrictions.
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Jason A. Liss, M.D. provided figure 1B and Ms. Susan Reeves prepared the composite figures.
9. Funding/Support
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
10. Financial Disclosure
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None to report
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Figure Legends
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Figure 1. A. Upon admission there was mild (1+) upper and lower eyelid edema on the right side with erythema and no warmth. There was moderate (2+) left upper eyelid edema with
ecchymosis; severe (3+) left lower eyelid and left facial edema, erythema, and induration but no
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warmth; and an area of abraded necrotic skin close to the lower eyelid margin. B. The
inflammatory signs worsened over the next day, and there was purulent discharge from the left
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lower eyelid and an abscess and necrosis of the lower eyelid skin.
Figure 2. Coronal (A), saggital (B), and axial (C) computed tomography revealed pre-septal and soft tissue edema (arrowheads) on the left side but no signs of orbital involvement, no orbital
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fractures, and no drainable abscess in the anterior left lower eyelid.
Figure 3. Skeletal muscle (A; hematoxylin and eosin, bar = 50 µm) and fascial connective tissue
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(B; hematoxylin and eosin, bar = 50 µm) were infiltrated by neutrophils and macrophages, accompanied by extensive necrosis and areas with numerous bacterial cocci causing a stippled
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appearance in the hematoxylin and eosin stained sections (C; hematoxylin and eosin, bar = 10 µm). Rare vessels (arrow) contained fibrin thrombi (D; hematoxylin and eosin, bar = 50 µm).
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