Preseptal and orbital cellulitis in otherwise healthy children and youth

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Epidemiology, definitions, and pathogenesis

Orbital infections are uncommon but important infections in childhood^[1]-[3]. They are classically divided into preseptal (when cellulitis affects tissues anterior to the orbital septum) or orbital (when tissues posterior to the orbital septum are involved)^[4][5]. Differentiating preseptal from orbital cellulitis is important due to their different etiologies, underlying mechanisms, prognoses, and associated complications. Preseptal (periorbital) cellulitis occurs most commonly in children younger than 5 years old and can be either traumatic or atraumatic. Traumatic preseptal cellulitis follows bacterial superinfection of non-intact skin, while the atraumatic form typically arises as a complication of bacterial rhinosinusitis^[6], or from meibomian gland or lacrimal sac infection, or (though rarely) hematogenous spread.

In orbital cellulitis, the lamina papyracea, a paper-thin bone that serves as both the medial wall of the orbit and the lateral wall of the ethmoid sinus, is dehisced by bacteria causing ethmoid sinusitis^[7]. The split allows bacterial access to the subperiosteal space and orbital compartment. Due to proximity, the maxillary and frontal sinuses can also become involved. The Chandler classification system is used to describe complications of sinusitis as follows: (1) inflammatory edema (preseptal cellulitis), (2) orbital cellulitis, (3) subperiosteal abscess, (4) orbital abscess, and (5) cavernous sinus thrombosis^[8]. Additional complications include Pott’s puffy tumour (subperiosteal abscess overlying frontal bone osteomyelitis), and intracranial extension with meningitis and empyema^[5].

Microbiology

Historically, Haemophilus influenzae type b (Hib) was the organism most often implicated in atraumatic preseptal and orbital cellulitis^[9]. However, since the introduction of the Hib vaccine, the incidence of orbital cellulitis due to Hib has decreased^[2][10][11]. Today, the bacteria involved in atraumatic preseptal and orbital disease in children mirror those of acute bacterial rhinosinusitis, typically involving streptococci (Streptococcus pneumoniae, pyogenes, and anginosus groups) and, to a lesser extent, Hib when children are underimmunized or living in an area where Haemophilus influenzae type A (Hia) is prevalent (e.g., in Canada’s Arctic or in some Indigenous communities)^[12][13].

In older children and adolescents, who are more prone to chronic bacterial sinusitis than young children, polymicrobial cultures containing streptococci and Staphylococcus aureus are common, and “oral” anaerobes can occasionally be recovered^[14]-[16]. While rates of methicillin-resistant S. aureus (MRSA) colonization are rising in the United States^[17], they remain generally low in Canada^[18]. MRSA rates vary across this country, however, and may be more common in young people with risk factors and in certain populations (e.g., Indigenous Peoples, newcomers to Canada from high-prevalence countries, and individuals residing near the US border where cross-border travel is frequent)^[19]-[21]. While frequently relied upon, risk factors cannot predict MRSA status in the era of community-associated MRSA^[20][22]. However, negative MRSA screening swabs can rule out MRSA colonization and infection with consistency^[22][23].

Clinical manifestations

In preseptal cellulitis, there is often history of a scratch or insect bite resulting in a skin infection with cellulitis^[4][24]. Key findings include unilateral eyelid erythema, edema, pain, and tenderness to touch, which can spread to the eyebrow, forehead, and cheek (Table 1)^[25][26].

In orbital cellulitis, there may be a preceding viral illness, sinusitis, trauma, odontogenic infection, or facial cellulitis^[4]. Children present with erythema and eyelid swelling but may also have pain or be experiencing limited extraocular movement, proptosis, chemosis, diminished visual acuity, diplopia, or a relative afferent pupillary defect (RAPD)^[17]. Children can also be ill-appearing, febrile, and appear toxic, which are less common presentations in preseptal cellulitis.

Most immunized children with preseptal cellulitis can be managed as outpatients, while children with severe preseptal cellulitis or suspected or confirmed orbital cellulitis should be hospitalized for diagnostic testing, antimicrobial therapy, and subspecialist involvement^[27][28].

Differential diagnosis

Other conditions that can present with a swollen, erythematous eye include infectious and non-infectious conditions such as bug bite, allergic reaction, chemical irritation, trauma, hordeolum/chalazion, dacrocystitis, conjunctivitis, or dermatitis. Less common systemic processes with orbital manifestations include idiopathic orbital inflammatory disease, intra-ocular masses or tumours (retinoblastoma, lymphoma, rhabdomyosarcoma, Langerhans cell histiocytosis), thyroid eye disease, and Kawasaki disease^[29]-[32].

Diagnostic testing and imaging

Well-appearing children with uncomplicated preseptal cellulitis do not require investigation^[24]. However, in children with severe infections, where diagnostic uncertainty exists regarding the extent of infection (i.e., preseptal versus orbital) or when examination is limited (e.g., in young children), a complete blood count and C-reactive protein (CRP) should be considered^[33]. Previous studies have associated elevated white blood count (WBC), absolute neutrophil count (ANC), and CRP with more severe infections, including a subperiosteal or orbital abscess (or both)^[28][34]. Blood cultures should be obtained in children with more severe disease to help guide definitive therapy. Conjunctival swabs are not recommended due to high rates of contamination.

Cross-sectional imaging, preferably a computerized tomography (CT) scan of the orbits and sinuses, with and without contrast, is the gold standard for diagnosis, but its main utility is to identify individuals who require surgery or have complications (e.g., cavernous sinus thrombosis), or to resolve diagnostic uncertainty^[11]. Consider a CT scan in children and youth who appear toxic, have findings suggestive of optic nerve involvement (i.e., abnormal vision, RAPD) or intracranial extension (i.e., neurological deficits, seizures), prominent forehead swelling, or who have risk factors associated with surgical intervention (e.g., CRP >120 mg/L, WBC >20,000/μL, or ANC >10,000/mm³)^[28][34][35]. Without risk factors, it is reasonable to delay the CT scan for 24 to 36 hours to assess response to antimicrobial therapy, especially when subspecialty consultation by otolaryngology and ophthalmology are readily available. Additional imaging, such as a repeat CT scan or magnetic resonance imaging (MRI), should be guided by the clinical picture and subspecialty input.

Antimicrobial therapy

Most children with preseptal or orbital cellulitis will be mildly to moderately unwell, with low risk for intracranial and visual complications. Therefore, a targeted approach to empiric antimicrobial therapy should be taken based on clinical presentation, immunization status, and local epidemiology/antimicrobial resistance patterns (Table 2)^{[33][36]-[39]}. Children who are systemically unwell or show signs of intracranial extension or compromised optic nerve function should be treated with broad spectrum, central nervous system-penetrating antibiotic therapy, and assessed for surgical intervention.

There has been an increasing tendency to add dedicated antibiotic coverage for staphylococci and anaerobes to standard therapy, although evidence that these antibiotics lead to changes in clinical outcomes is lacking^[37]. A recent Canadian study of 1421 hospitalized children and adolescents with orbital infections found that S. anginosus and S. pyogenes were the most common organisms recovered, for which an aminopenicillin may be sufficient^[18]. A previous study suggested that staphylococci and anaerobes are often isolated in older children and those with chronic sinusitis^[14], though a recent study has found no association between microbiology and age^[40], and most “oral” anaerobes are penicillin-susceptible^[41].

In children and youth with chronic sinusitis or more severe infections, coverage of S. aureus (including MRSA when suspected) is reasonable. While non-typeable H. influenzae bacteria are increasingly isolated in acute otitis media and sinusitis, they are not typically isolated from orbital abscesses^[42]. Coverage with a beta-lactam/beta-lactamase inhibitor combination (i.e., amoxicillin-clavulanate) is reasonable to treat cases of:

• orbital cellulitis
• atraumatic preseptal cellulitis that fail to improve with narrower initial empiric antibiotic therapy, and
• in children who are underimmunized against Hib or living in areas where Hia is common.

Some experts suggest using ampicillin or cefazolin as empiric therapy for orbital cellulitis arising from acute or chronic sinusitis respectively in immunized older children and youth, and this strategy is reflected in the local treatment guidelines of one Canadian children’s hospital^[43].

Evidence regarding duration of antimicrobial therapy is limited^[44]. General recommendations include 5 to 7 days for preseptal cellulitis, 10 to 14 days for uncomplicated orbital cellulitis, and 2 to 3 weeks for orbital cellulitis with subperiosteal or orbital abscess but no intracranial involvement. Individuals showing clinical improvement can be transitioned from intravenous (IV) to oral antibiotics. Choice of oral antibiotic therapy should be guided by results of cultures and MRSA screening swabs, when available.

For children and youth who are systemically unwell, have not responded to initial therapy, or who have a large subperiosteal or orbital abscess, or intracranial extension, consultation with an infectious diseases (ID) specialist should be sought.

Adjunctive agents and surgical intervention

Children with suspected orbital cellulitis complicated by a subperiosteal or orbital abscess should be evaluated promptly by an otolaryngologist and ophthalmologist for possible surgical intervention, while those with intracranial complications should be evaluated by a neurosurgeon. Most subperiosteal collections do not require drainage^[45].

Routine use of intranasal corticosteroids to improve symptom resolution is based on weak evidence from studies conducted in adolescents and adults with sinusitis^[46][47]. Intranasal decongestants and saline are also routinely used for the same purpose though with limited supporting evidence. Finally, limited evidence supports the routine use of systemic corticosteroids to reduce complications and improve outcomes in orbital cellulitis^[48][49].

Practice points

• Preseptal cellulitis usually presents with unilateral eyelid erythema, edema, and tenderness to touch, while orbital cellulitis presents with limited or painful extra-ocular movements, proptosis, chemosis, diminished visual acuity, or a relative afferent pupillary defect.

• Consider computed tomography (CT) scan with and without contrast in young children, those who appear toxic, have red flags suggestive of optic nerve involvement or intracranial extension, or with prominent forehead swelling, a high white blood cell (WBC) count or C-reactive protein (CRP), or in cases of diagnostic uncertainty. Otherwise, consider delaying imaging pending clinical response to antimicrobial therapy.

• Children with orbital cellulitis complicated by a subperiosteal or orbital abscess should be evaluated promptly by an otolaryngologist and ophthalmologist for possible surgery.

• Antibiotic choice and duration for paediatric orbital infections depends on the anatomic sites involved, immunization status, and the presence of risk factors for methicillin-resistant Staphylococcus aureus (MRSA) or Haemophilus influenzae type a.

• The use of intranasal corticosteroids and intranasal saline should be guided by subspecialty input. There is insufficient data to recommend the routine use of systemic corticosteroids.

Acknowledgement

This practice point was reviewed by the Acute Care, Community Paediatrics, and Infectious Diseases and Immunization Committees of the Canadian Paediatric Society.

CANADIAN PAEDIATRIC SOCIETY HOSPITAL PAEDIATRICS SECTION EXECUTIVE (December 2023)

Members: Melanie Buba MD (President), Sepideh Taheri MD (President-Elect), Sidd Thakore MD (Past President), Geert 't Jong MD PHD (Secretary-Treasurer), Peter Gill MD DPhil MSc (Member at Large), Jennifer Lee Wiebe MD (Member at Large)
Principal authors: Peter J. Gill MD DPhil MSc, Melanie Buba MD, Carsten Krueger MD, Nikolaus Wolter MD MSc, Yohann Arunun Reginald MBBS

Funding
There is no funding to declare.

Potential Conflict of Interest
The authors have indicated they have no conflicts of interest.

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