A Clinical guide to pediatric infectious disease

8

Periorbital and Orbital Cellulitis

The red, swollen eye is a common presenting symptom in pediatrics. As is the case for many pediatric infections, there are three mechanisms of disease for the red eye. Each of these mechanisms involves different presenting symptoms, different causative pathogens, and different management strategies.

Mechanism of Direct Inoculation

This process involves introduction of a pathogen into the eye or the soft tissue surrounding the eye. In the former, one develops viral or bacterial conjunctivitis. In the latter case, one develops a periorbital cellulitis.

Ophthalmia Neonatorum

Epidemiology and Etiology

Ophthalmia neonatorum is defined as conjunctivitis in the first weeks of life. Neisseria gonorrhoeae and Chlamydia trachomatis infections are the most common causes of neonatal conjunctivitis. N. gonorrhoeae infection in the newborn infant typically involves the eyes and is caused by exposure at the time of delivery.

Chlamydia trachomatis is the other major pathogen of neonatal conjunctivitis. As with gonococcal disease, exposure is at the time of delivery. The risk for conjunctivitis to a baby who is exposed is about 50%, with 20% of exposed infants eventually developing pneumonia.

Presentation

Neonates usually present during the first weeks of life with a purulent conjunctivitis. Disease attributable to C. trachomatis is often not as severe as that caused by N. gonorrhoeae and may present later in the neonatal period.

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Diagnosis

Gram stain of the conjunctival discharge may reveal gram-negative diplococci. Newborns with N. gonorrhoeae disease should have cultures of blood and spinal fluid because disseminated disease can occur.

Neonatal C. trachomatis conjunctivitis can be diagnosed by the appearance of intracytoplasmic inclusions on Giemsa stain of conjunctival scrapings. There is considerable variation in the sensitivity of this test up to 90%, depending on collection technique and laboratory experience with conjunctival specimens. Direct fluorescent antibody and polymerase chain reaction testing for Chlamydia antigen are also used on conjunctival scrapings in patients suspected of having C. trachomatis infection.

Management

Ceftriaxone is the therapy of choice for gonococcal infections because an increasing number of isolates are showing resistance to penicillin. Infants with gonococcal conjunctivitis need frequent eye irrigation because the purulent discharge is very damaging to the cornea and can result in permanent scarring.

Chlamydia trachomatis

Treatment of infants with C. trachomatis conjunctivitis is always with oral erythromycin, 50 mg/kg per day in four divided doses for 2 weeks. Topical treatment of C. trachomatis conjunctivitis is not recommended; systemic treatment is needed to prevent subsequent development of lower respiratory tract disease.

For newborns diagnosed with either gonococcal or chlamydial conjunctivitis, evaluation for other sexually transmitted diseases, including syphilis, hepatitis B, hepatitis C, and human immunodeficiency virus (HIV) infection, should be considered.

Conjunctivitis in Toddlers

Epidemiology and Etiology

The etiologic agents of pediatric conjunctivitis were investigated for the first time in the 1980s. About 80% of cases were found to be bacterial in origin. Nontypeable Haemophilus influenzae was recovered in almost half of cases; Streptococcus pneumoniae was the other common bacterial agent. Adenovirus was the most common viral pathogen isolated.

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Presentation

Distinguishing viral from bacterial conjunctivitis clinically can be difficult. Bacterial conjunctivitis typically affects children younger than 5 years of age. Children present with a purulent discharge that often causes the eyelids to be stuck together after a night's sleep. Adenoviral conjunctivitis often occurs in the fall and winter and usually in children older than 6 years of age. It can be associated with sore throat and low-grade fever. Adenovirus is very contagious, and epidemics involving athletic groups or persons with common exposure to water or fomites are well described. Adenovirus conjunctivitis can also cause a symptom that may mimic a bacterial periorbital infection. Although older children with adenovirus conjunctivitis may have minimal eyelid swelling, younger children may exhibit considerable edema and swelling that can appear very similar to bacterial periorbital cellulitis.

Diagnosis

Reviews have noted that an inflammatory membrane on the conjunctiva is a consistent physical finding for adenovirus conjunctivitis and can be helpful in the diagnosis.

An additional concern is that acute adenoviral conjunctivitis, with its associated fever and pharyngitis, may mimic Kawasaki syndrome. Studies have shown that children with acute adenoviral infection are likely to have purulent conjunctivitis, lower levels of alanine amino transferase, and lower sedimentation rates. A rapid antigen test for adenovirus done on a conjunctival swab can be helpful in distinguishing adenoviral conjunctivitis from Kawasaki syndrome.

Management

Pediatricians often empirically treat conjunctivitis with antibacterial agents. This approach seems reasonable, given the high incidence of bacteria causing acute conjunctivitis. Attempts to have formal laboratory diagnosis can include obtaining Gram stain and culture of the purulent discharge or conjunctival scrapings. It has been found that Gram stain and cultures of conjunctival scrapings obtained by ophthalmologists have a higher yield than cultures of conjunctival exudate. Most pediatricians are not experienced in obtaining conjunctival scrapings, although Gram stain of conjunctival exudate showing more than 15 white blood cells per high-power field may be helpful in distinguishing bacterial from viral conjunctivitis.

Although acute bacterial conjunctivitis is known to be a self-limited disease, double-blind placebo-controlled studies have shown that treatment with either topical or oral antibiotics resulted in earlier clinical improvement and earlier eradication of bacteria from the conjunctivae. It is for this reason that bacterial conjunctivitis is usually treated.

There are a variety of topical antibiotics available, including trimethoprim, polymyxin B, gentamycin sulfate, and sodium sulfacetamide. Also now available are the topical fluoroquinolones, approved for children older than 1 year. It has been

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suggested in the past that if first-line topical therapy for acute conjunctivitis is not successful, one should consider obtaining a culture and consider using a topical fluoroquinolone to address the possibility of a resistant pathogen. A recent report measured increasing antibiotic resistance in bacteria isolated from children with bacterial conjunctivitis; β-lactamase production was detected in almost 70% of strains ofH. influenzae; over one third of S. pneumoniae isolated were penicillin nonsusceptible (minimal inhibitory concentration [MIC] > 0.10 µg/mL). This increasing resistance might alter the efficacy of some of the frequently used topical antibiotics. There thus continues to be debate on the optimal use of topical agents in the treatment of bacterial conjunctivitis. Many ophthalmologists now avoid the aminoglycoside or sulfa-containing agents, reporting that they often hurt when applied and frequently have lower efficacy against the increasingly resistant pathogens. These specialists often recommend proceeding directly to a topical fluoroquinolone if treatment is to be offered.

Otitis-Conjunctivitis Syndrome

In the early 1980s, it was recognized that there was a unique pediatric syndrome of conjunctivitis and otitis media.

Etiology

The pathogen in this clinical syndrome is thought to be nontypeable H. influenzae.

Presentation

Children usually present after development of conjunctivitis with low-grade fever and mild respiratory symptoms. Several days later, otitis media becomes apparent, usually with the development of ear pain.

Diagnosis

Diagnosis is made by the typical history and documentation of otitis media closely following an episode of conjunctivitis.

Management

The treatment of the otitis-conjunctivitis syndrome has also been the subject of considerable investigation. About 25% of children who present with H. influenzae conjunctivitis who are treated topically ultimately develop otitis media. In one study, the administration of ampicillin to patients presenting initially with purulent conjunctivitis alone resulted in fewer episodes of secondary otitis media. Interestingly, a subsequent study using cefixime did not show a similar benefit in preventing otitis media. Patients who present with both otitis and conjunctivitis at initial

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evaluation deserve systemic therapy, typically an oral antibiotic that covers β-lactamase–producing H. influenzae. Some recommend that oral antibiotics be used in children who present with bacterial conjunctivitis and who are considered at high risk for otitis media (i.e., young age, attendance at daycare). If systemic therapy is given, topical therapy is not needed.

Periorbital Cellulitis

Epidemiology and Etiology

Direct inoculation of pathogens into the skin and soft tissue around the eye are common. Bacterial pathogens may be introduced secondary to insect bite or mild trauma with resultant periorbital cellulitis. Organisms most frequently causing these infections are Streptococcus pyogenes and Staphylococcus aureus.

Presentation

Affected children present with periorbital cellulitis and swelling. Frequently, there is a readily observed cut or break in the skin accompanied by impetiginous lesions about the face. Extraocular movements are typically normal.

Diagnosis

Diagnosis is based on the physical examination. A culture of an accompanying discharge from a cut or area of trauma may yield the responsible pathogen.

Management

If this mechanism is suspected, antibiotic therapy should be geared to these particular organisms. Clindamycin or a first-generation cephalosporin offers good coverage.

Mechanism of Hematogenous Spread

Epidemiology and Etiology

Periorbital cellulitis can also occur when periorbital regions become seeded during bacteremia.

The classic bacteria associated with bacteremic periorbital cellulitis are H. influenzae, (type b) and S. pneumoniae. It is thought that there is a predilection for

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these bacteremic organisms to deposit within the periorbital area; it is also possible that sinusitis with either of these organisms can infect periorbital regions as a result of venous congestion and decreased lymphatic flow.

Presentation

Bacteremic patients often present in the first 5 years of life. They have periorbital cellulitis and swelling, although there is no obvious cut or area of inoculation.

Diagnosis

Yield of blood cultures in bacteremic periorbital cellulitis is about 25%. The diagnosis is often suspected in a child with periorbital cellulitis and no obvious signs or history of preceding trauma.

Management

In a child younger than 5 years of age with periorbital cellulitis in whom there is no obvious trauma, antibiotic coverage should include those agents active against either H. influenzae or S. pneumoniae. Second- or third-generation cephalosporins are adequate for this purpose. The conjugate vaccine for H. influenzae has led to a great decrease in the incidence of Haemophilus disease; it is also possible that the introduction of the Prevnar vaccine will cause a similar decrease in pneumococcal bacteremia and subsequent pneumococcal periorbital cellulitis.

A common question arises regarding the need for lumbar puncture in patients with presumed hematogenous periorbital cellulitis. These patients may be at risk for meningitis because the bacteremia that has localized in the periorbital regions may also have seeded in the cerebrospinal fluid. The rate of concurrent meningitis seen with H. influenzae periorbital cellulitis is about 5%. Lumbar puncture is recommended in younger children, especially those younger than 12 months of age and those with associated irritability or meningeal findings. Any abnormal findings on cerebrospinal fluid, such as a pleocytosis with neutrophil predominance, warrants treatment of presumed meningitis.

Mechanism of Contiguous Spread (Orbital Cellulitis)

Epidemiology and Etiology

The ethmoid sinuses form the medial walls of the orbit. Children with significant ethmoid sinusitis may have spread of infection into the orbit. The organisms involved in such cases are the organisms of sinusitis; S. aureus, group A streptococcus, S. pneumoniae, H. influenzae, and anaerobic bacteria.

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Presentation

Typically, the patient with orbital cellulitis is older. There is no evidence of direct inoculation. Parents often give a history of a preceding sinus infection. There is often proptosis and limitation of the extraocular movements.

It is important to realize that periorbital cellulitis is caused by a different mechanism than orbital cellulitis and thus will not progress to orbital cellulitis. A comparison of the features of periorbital and orbital cellulitis can be found in Table 8.1.

In a child with a red swollen eye and an exam consistent with contiguous spread from a sinus infection, evaluation for extension into the orbit is essential. It is important to remember that purulent infection can spread into the orbit and affect orbital structures, particularly the optic nerve.

Diagnosis

Examination should determine whether there is proptosis or a decrease in extraocular movements. Visual acuity should, if possible, be tested. It is understood that in patients with this condition, the eye can be swollen to such an extent that examination can be difficult. In this case, the radiographic procedure of choice is computed tomography (CT) of the orbit. This exam will show clearly the orbital structures and the presence of orbital disease (Fig. 8.1).

Management

A useful staging system has been published for orbital cellulitis (Chandler's criteria). As in many staging criteria, the identification of a particular stage has been correlated with the need for particular management.

TABLE 8.1. Periorbital Versus Orbital Cellulitis

1. Periorbital cellulitisa.

1. <5 years

2. Mechanism

1. Trauma

2. Bacteremia

3. Ocular motility not affected

4. Organisms
   1. Trauma         Streptococcus pyogenes
                           Staphylococcus aureus
   2. Bacteremia   Streptococcus pneumoniae

5. Progression to orbital disease does not occur

2. Orbital cellulitis

1. >12 years

2. Mechanism—sinusitis

3. Ocular motility may be reduced

4. Organism   S. pneumoniae
                  Nontypeable Haemophilus species
                  Moraxella catarrhalis
                  S. aureus

5. Treatment may include surgical drainage

 

FIG. 8.1. Computed tomography scan of orbit showing left orbital abscess.

Chandler's Stages of Orbital Cellulitis

Stage 1: Periorbital cellulitis. Eyelid swelling with sinusitis. No intraocular disease.
Stage 2: Edema of the orbital lining with proptosis and limitation of extraocular movement. No subperiosteal abscess seen within orbit.
Stage 3: Visual loss, progression of changes seen in stage 2, with subperiosteal abscess and globe displacement within orbit.
Stage 4: Ophthalmoplegia with visual loss. CT scan shows proptosis and abscess formation involving the extraocular muscles and orbital fat.

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Traditionally, Chandler's stage 4 orbital cellulitis had been considered a surgical condition. Recently, case studies have been collected that suggest that even patients with well-defined subperiosteal abscesses may respond to intravenous antibiotics without the need for surgical drainage. Antibiotics to cover all possible organisms would include nafcillin and a third-generation cephalosporin. Clindamycin can be substituted for nafcillin because it is effective against S. pneumoniae and S. aureus and also provides coverage for anaerobic bacteria. Another possible choice is ampicillin-sulbactam (Unasyn). Most specialists believe that patients with significant intraorbital abscesses need close monitoring. Serial examination, including assessment of vision, extraocular muscle function, and repeat

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CT, are mandatory. Failure to improve within 24 to 48 hours remains an indication for surgical drainage. Because the mechanism of infection includes extension through the ethmoid sinus, many infectious disease specialists recommend treating orbital cellulitis as an osteomyelitis. A minimum of 21 days of therapy is recommended (Table 8.2).

TABLE 8.2. Management of the Swollen Eye

1. Conjunctivitis

1. Ophthalmia neonatorium

1. Pathogens: Neisseria gonorrhoeae
                 Chlamydia trachomatis

2. Treatment: Ceftriaxone, 50–75 mg/kg/d in 1 or 2 divided doses. Oral erythromycin needed (50 mg/kg/d in 4 divided doses) if C. trachomatis is present

2. Bacterial conjunctivitis (toddlers)

1. Pathogens: Nontypeable Haemophilus influenzae
                 Streptococcus pneumoniae
                 Adenovirus

2. Topical treatment: Polytrim (trimethoprim sulfate and polymyxin)
                           Gentamycin sulfate
                           Sodium sulfacetamide
                           Ciprofloxacin (Ciloxan)

3. Otitis–conjunctivitis syndrome

1. Pathogen:    Nontypeable H. influenzae

2. Treatment:  Amoxicillin-clavulanate (Augmentin)
                  Oral second- or third-generation cephalosporins

2. Periorbital cellulitis (bacteremic spread)

1. Pathogens: H. influenzae, type b
                 S. pneumoniae

2. Treatment: second- or third-generation cephalosporins

3. Orbital cellulitis (contagious spread)

1. Pathogens: H. influenzae, S. pneumonia, Staphylococcus aureus, anaerobes

2. Medical treatment

1. Unasyn (ampicillin-sulbactam), 100–200 mg/kg/day of ampicillin component

2. Clindamycin, 40 mg/kg/d in three divided doses in combination with third-generation cephalosporin

3. Surgical drainage should be strongly considered

Selected Readings

Block SL, Hedrick J, Tyler R, et al. Increasing bacterial resistance in pediatric acute conjunctivitis (1997–1998). Antimicrob Agents Chemother 2000;44(6):1650–1654.

Givner LB. Periorbital versus orbital cellulitis. Pediatr Infect Dis J 2002;21(12):1157–1158.

Harrison CJ, Hedrick JA, Block SL. Relation of the outcome of the conjunctivitis-otitis syndrome to identifiable risk factors and oral antimicrobial therapy. Pediatr Infect Dis J 1987;(6):536–540.

Ruttum MS, Ogawa G. Adenoviral conjunctivitis mimics preseptal and orbital cellulitis in young children. Pediatr Infect Dis J1996;15(3):266–267.

Starkey CR, Steele RW. Medical management of orbital cellulitis. Pediatr Infect Dis J 2001;20(10)1002–1005.

Teoh DL, Reynolds S. Diagnosis and management of pediatric conjunctivitis. Pediatr Emerg Care 2003;19(1):48–55.

Wald ER. Conjunctivitis in infants and children. Pediatr Infect Dis J 1997;16:[2 Suppl]S17–20.