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Ophthalmia Neonatorum
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Conjunctivitis in newborn infants (first 28 days of life) is not uncommon (Table 98-1). Because of the potential complications from ocular infections in infancy, neonates with symptoms mandate a thorough evaluation. Important guidelines for evaluation include the following:
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Obtaining a detailed maternal history including prenatal care, history of or exposure to venereal disease, duration of rupture of membranes, type of delivery, agent used for ocular prophylaxis at birth, recent exposure to conjunctivitis, and timing of onset of symptoms. History should also include a description of excessive tearing, type and amount of exudate, and elucidation of systemic signs of illness in the baby, such as fever, vomiting, irritability, or lethargy.
Physical examination must be thorough, including a comprehensive eye examination searching for evidence of eyelid erythema, edema, discharge, corneal ulceration, globe perforation, or foreign body. In addition, general physical examination must be complete; special attention must focus on the skin, respiratory, and genitourinary system for evidence of concomitant systemic involvement.
Conjunctival scrapings should be obtained for Gram stain, Giemsa stain, and viral and bacterial cultures including Neisseria. A rapid antigen test is sensitive and specific for Chlamydia and can be obtained easily from the conjunctiva. Culture is usually not necessary. Multiplex PCR is now available at many centers to test for viruses such as Herpes Simplex Virus (HSV) 1 and 2, Human herpes virus 6 (HHV-6), cytomegalovirus (CMV) Ebstein–Barr Virus (EBV), and Varicella zoster virus (VZV), all of which can cause a conjunctivitis. Studies have shown that use of fluorescein and topical anesthetics may reduce the accuracy of PCR tests. The eye should be rinsed with saline after the use of these agents and before PCR samples are obtained.3
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Differential Diagnosis
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Chemical Conjunctivitis
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Chemical conjunctivitis caused by silver nitrate drops in the immediate newborn period occurs in almost 10% of newborns. Signs of this type of conjunctivitis include bilateral conjunctival hyperemia and mild discharge that begin in the first 24 hours of life and usually subside within 48 hours. Gram stain reveals no organisms and only a few white blood cells. The inflammation is typically quite mild and does not require intervention.
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Chlamydia Trachomatis
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Chlamydia infections have a typical incubation period of 1 to 2 weeks, but can occur earlier if there was premature rupture of membranes. Onset of symptoms may be delayed in babies who received prophylaxis at birth. Typically, the conjunctiva becomes hyperemic and edematous with the palpebral conjunctiva more involved than is the bulbar conjunctiva. Unilateral, purulent involvement is characteristic. Neonates may also have evidence of a concomitant otitis media or afebrile pneumonia. Samples are obtained by scraping the palpebral conjunctiva of the lower lid. The diagnosis is confirmed by identification of chlamydial antigen, detection of intracellular inclusions from Giemsa stain, or isolation of the organism. Antigen detection tests are rapid, sensitive, and specific and are the most efficient means of confirming the diagnosis. Gram stain is not helpful in confirming the diagnosis.
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Systemic therapy is absolutely essential in the treatment of this condition. The treatment of choice is oral erythromycin (40–50 mg/kg/d) for a 2- to 3-week course to eliminate both conjunctival and nasopharyngeal colonization. Administration of a topical agent is unnecessary. Since chlamydia is the most frequent sexually transmitted disease, prevention by detection of infection in the mother prior to delivery is essential. Treatment of the affected infant's mother and her partner(s) is also recommended. Early studies suggested that the administration of erythromycin ointment prophylaxis in newborns was effective in preventing chlamydia conjunctivitis but not in altering the rate of development of pneumonia or nasopharyngeal infection. Subsequent studies have revealed that neonatal ocular prophylaxis with erythromycin does not reduce the incidence of chlamydial conjunctivitis. Chlamydial conjunctivitis can lead to chronic changes such as conjunctival scarring and micropannus formation. Fortunately, these long-term ocular sequelae are quite rare. In some cases, chlamydial conjunctivitis may resolve spontaneously without treatment; however, these infants are at risk for reoccurrence of infection involving not only the eyes, but the pharynx, rectum, and lungs as well.
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Bacterial Conjunctivitis
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The role of other bacteria in the newborn period is not quite as clear and can be caused by S. aureus, Haemophilus spp., S. pneumoniae, and Enterococci. Many studies have also shown that these bacteria, in addition to Corynebacterium, Propionibacterium, Lactobacillus, and Bacteroides can be normal flora. Typically, the conjunctiva is red and edematous with some amount of exudate. Diagnosis is made by Gram stain and culture. Broad-spectrum topical antimicrobial therapy is initiated. Untreated cases of bacterial conjunctivitis could potentially progress to corneal ulceration, perforation, endophthalmitis, and septicemia.
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Neisseria Gonorrhoeae
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Historically, gonococcal ophthalmia neonatorum has been of greatest concern because of its serious complications. In the early 1900s, approximately 25% of children admitted to American schools for the blind acquired their disability from N. gonorrhoeae. By the late 1950s, 0.5% were blind as a result of Neisseria. With the onset of antibiotics and postnatal prophylaxis, the current incidence in the United States is thought to be 2 to 3 cases per 10,000 live births. The mean incubation period is 6.5 days with a range of 1 to 31 days. Gonococcal ophthalmia neonatorum classically presents as a purulent, bilateral conjunctivitis. Conjunctival hyperemia, chemosis, eyelid edema, and erythema may also be seen. This entity is diagnosed by Gram stain, revealing gram-negative intracellular diplococci. Cultures should be sent immediately on blood and chocolate agar, because the organisms die rapidly at room temperature. Cultural growth usually occurs within 2 days. Infants with conjunctivitis may have other manifestations of localized disease including rhinitis, anorectal infection, arthritis, and meningitis. Neonates with suspected gonococcal conjunctivitis or any neonate with fever and conjunctivitis should have a sepsis evaluation, including a lumbar puncture. Gonococcal conjunctivitis is considered an ophthalmologic emergency.
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Treatment must be systemic. Neonates without meningitis should be treated for 7 days with either ceftriaxone or cefotaxime. If meningitis is present, treatment continues for 10 to 14 days. If the organism is sensitive to penicillin, penicillin G can be substituted. Treatment must also include frequent saline irrigation of the eyes. Parents should be screened for gonococcal disease. An infant born to a mother with known active gonococcal infection should receive one dose of ceftriaxone immediately after delivery.
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Most neonates with herpes simplex become colonized during the birth process. Neonatal herpes simplex may occasionally present first as conjunctivitis. The onset is generally 2 to 14 days after birth. Characteristics are not clinically distinctive; however, unilateral or bilateral epithelial dendrites are virtually diagnostic. Fluorescein staining reveals these defects. Parental history of herpes is important to obtain. Often conjunctivitis leads to further disseminated infections that carry a high morbidity and mortality rate. The conjunctivitis can be diagnosed with conjunctival scrapings looking for multinucleated giant cells and intranuclear inclusions. A fluorescent antibody test should be obtained followed by a viral culture.
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Treatment should consist of intravenous acyclovir (30 mg/kg/day divided q8h IV for 14 to 21 days for neonates, 3 months–12 years: 20 mg/kg/dose IV q8h for 10 days) and topical trifluorothymidine (≥6 years: 1 drop onto cornea q2h) while awake until re-epithelialization (not to exceed 9 gtt/d), then 1 drop q4h (minimum 5 drops/d) for 7–21 days. Parents must be aware of the high risk of recurrence of keratitis later in life; an ophthalmologist should follow these children closely. Recurrences are treated with topical therapy alone. Neonatal herpes simplex can lead to the development of keratitis, cataracts, chorioretinitis, and optic neuritis in addition to numerous other ocular problems.
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Viral Etiologies (Nonherpetic)
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Other viral causes of conjunctivitis in neonates are infrequent. Conjunctivitis in a sibling or parent is the most likely source of infection. Hands or fomites are the modes of transmission. Diagnosis is made by history of recent exposure and clinical findings. Usually infections are self-limited. Education regarding hand-washing and not sharing of washcloths and towels is necessary.
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Obstructed Nasolacrimal Duct
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Congenital nasolacrimal duct obstruction, or dacryostenosis, is often only recognized when infants have a history of recurrent ocular infections. The blockage is frequently caused by failure to canalize a membrane called the valve of Hasner, which is located at the lower end of the nasolacrimal duct. Affected infants often have pooling of tears onto the lower lid and cheeks and maceration of the eyelids. Upon crying, tears fail to arrive at the external nares. It is important to differentiate nasolacrimal duct obstruction from congenital glaucoma. Congenital glaucoma presents with tearing, photophobia, and a cloudy, enlarged cornea. Redness is not a major feature of nasolacrimal duct obstruction. Conservative treatment consists of massaging the lacrimal sac, suppressive topical antimicrobials, and warm compresses. Probing of the nasolacrimal system is not recommended until after 1 year of age because 95% of children younger than 13 months will experience spontaneous opening of the lacrimal duct (Fig. 98-4).
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Noninfectious Etiologies
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The differential diagnosis of the red eye in neonates should also include noninfectious etiologies. Corneal abrasions can be detected in infants and may often be secondary to a scratch from their fingernail. Conjunctival hyperemia may be present; fluorescein staining is diagnostic. Linear abrasions on the superior aspect of the cornea should alert the physician to an upper eyelid foreign body. Trauma to the eye during delivery can also cause a corneal abrasion or laceration.
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Conjunctivitis Beyond the Neonatal Period
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Conjunctivitis is a frequently encountered entity in children (Table 98-2).
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It is crucial to identify conjunctivitis from more serious conditions. Conjunctivitis in older children is characterized by normal vision, a gritty sensation in the eye, diffuse injection, and exudate. Photophobia and lacrimation are not usually associated with conjunctivitis. Keratitis and iritis typically are associated with impaired vision, true pain, photophobia, and lacrimation.
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Clinically, viral conjunctivitis is difficult to distinguish from bacterial conjunctivitis. Marked exudate, severe injection, and lid matting is more typical of bacterial or chlamydial infections. Preauricular adenopathy is often associated with viral infections. Follicles on the palpebral conjunctivae are more indicative of viral or chlamydial infections.
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Bacterial Conjunctivitis
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The bacteriology of conjunctivitis in children is expansive and includes Haemophilus aegyptius, S. pneumoniae, S. aureus, N. gonorrhoeae and meningitides, Escherichia coli, P. aeruginosa, Proteus spp., viridans streptococci, S. pyogenes, Corynebacterium diphtheria, Chlamydia trachomatis, and M. catarrhalis. Outbreaks of acute catarrhal conjunctivitis, also known as “pink eye,” may occur in day care or among school-age children. The offending organisms are most frequently S. pneumoniae or H. aegyptius. Outbreaks are more often seen in the winter months. The role of S. aureus in nontraumatic conjunctivitis is difficult to determine because it occurs frequently in asymptomatic patients. In addition, Haemophilus has been associated with concomitant otitis media, and subsequent studies have coined the term conjunctivitis-otitis syndrome when the two occur together. The otitis associated with this syndrome may be asymptomatic, but when detected should be treated with oral antibiotics. The addition of topical antibiotics may not increase efficacy of treatment.
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Pseudomonas is an infrequent pathogen that can cause an acutely advancing necrotizing picture, so it must be recognized and treated aggressively. Children with cystic fibrosis and those who wear contact lenses are at highest risk for infection with Pseudomonas. These patients should be evaluated by an ophthalmologist to assess for the presence of corneal ulceration. Although most types of acute bacterial conjunctivitis are self-limited, the use of topical antibiotic therapy is thought to more quickly eradicate the organism, thereby decreasing the amount of time patients are contagious. Routine Gram stain and culture usually is unnecessary unless there is a history of copious mucopurulent exudate (Neisseria) or a chronic history of conjunctivitis.4
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Treatment is empiric with topical antimicrobial ointments or ophthalmic drops. Specific drugs include tobramycin drops, ciprofloxacin drops or ointment, ofloxacin drops, polymyxin B sulfate drops, erythromycin ointment, azithromycin, trimethoprim-polymyxin drops, or gentamicin drops. Typical treatment is for 7 days, three to four times a day.
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Contact lenses can cause conjunctivitis and corneal abrasions. Lens wear should be discontinued; storage and cleaning solutions must be replaced to prevent further contamination. Topical antibiotics to avoid Pseudomonas or secondary bacterial infection may be initiated. An aminoglycoside such as tobramycin (Tobrex) drops or a fluoroquinolone such as ciprofloxacin (Ciloxan) or ofloxacin (Ocuflox) should be administered four times a day for 5 to 7 days. Corneal ulcers should always be considered in patients who wear contact lenses and have a red eye. These patients should be referred to an ophthalmologist.
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Adenoviruses are the most common cause of viral conjunctivitis in children. There are a few clinical syndromes associated with this group of viruses including pharyngoconjunctival fever, epidemic keratoconjunctivitis, and nonspecific follicular conjunctivitis. Pharyngoconjunctival fever is most common in children and is associated with an upper respiratory tract infection, regional lymphadenopathy, and fever. The illness is usually self-limited, lasting 1 to 2 weeks. Enteroviral infections from particular coxsackieviruses and echoviruses may cause conjunctivitis but are often associated with other clinical signs including rash or aseptic meningitis. Acute hemorrhagic conjunctivitis is caused by enterovirus 70 or coxsackie A24 and also occurs in epidemics. Transmission is by direct contact with an incubation of less than 2 days. Clinically, patients present with sudden onset of unilateral ocular redness, excessive tearing (epiphora), photophobia, pain, purulent discharge, and eyelid swelling, which develop in a span of 6 to 12 hours. Patients may complain of a burning pain often described as a foreign body. In 80% of the cases, the other eye becomes involved within 24 hours. Some patients develop subconjunctival hemorrhages, which are usually located beneath the superior bulbar conjunctiva. Malaise, myalgias, fever, headache, and upper respiratory tract symptoms may also accompany conjunctivitis. Conjunctival scrapings for a viral culture yield identification of the virus. Ophthalmologic sequelae are rare: <5% of cases develop a secondary bacterial conjunctivitis.
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Treatment is symptomatic with cool compresses. Many physicians prescribe a topical antimicrobial to prevent secondary bacterial infection, but this practice has not been proven to be effective. Patients with epidemic keratoconjunctivitis should be kept out of school for 2 weeks to prevent an outbreak.
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Herpes Simplex and Varicella-Zoster
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Vesicular lesions on the eyelid can be due to herpes simplex, varicella-zoster, impetigo, or contact dermatitis. Herpes simplex infections are characterized by unilateral, follicular conjunctivitis with vesicles localized to the eyelids. Preauricular lymphadenopathy is commonly present. Fifty percent of the patients develop keratitis within 2 weeks. The virus remains latent in the sensory ganglion and lacrimal glands. Approximately 25% of all children will have recurrences; these usually begin with corneal involvement. Long-term complications include necrotizing stromal disease, diffuse retinitis, and scarring. Herpes simplex is the most common cause of severe corneal ulceration in children and is second only to trauma as a cause of corneal blindness in children. Trifluorothymidine (≥6 years: 1 drop onto cornea every 2 hour) while awake until reepithelialization (not to exceed 9 gtt/d), then 1 drop q4h (minimum 5 drops/d) ×7 to 21 days is the preferred agent for the treatment of herpes simplex because of its increased solubility, diminished toxicity, and lack of viral resistance.5 Approximately 95% of the corneal ulcers treated with it are cured within 2 weeks; however, treatment should be extended for 1 additional week after resolution of the lesions. Rarely corneal debridement is required. For herpetic eye lesions, systemic acyclovir is not recommended because the drug does not penetrate the avascular cornea (Figs. 98-5 and 98-6).6
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Ocular involvement with varicella is relatively uncommon, occurring in <5% of cases. In chicken-pox, the conjunctiva can become involved through two mechanisms: eyelid vesicles can slough virus into the conjunctival cul-de-sac or vesicle formation can take place on the conjunctival surface. Occasionally, the cornea is involved. Fluorescein staining of the cornea and conjunctiva is necessary.
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Zoster is uncommon in children, with only 5% of all cases occurring in children younger than 5 years of age. Zoster infections of the eye notably follow the distribution of the first division of the trigeminal nerve. Lesions are usually located on the forehead and upper eyelid and can be located on the tip of the nose. Varicella and zoster conjunctivitis may be treated with oral acyclovir.
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Neisseria Gonorrhoeae
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Gonococcal eye infections can occur in prepubertal children. A nonvenereal mode of transmission has been suggested. Intravenous antibiotics are still recommended for this age group.
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Gonococcal conjunctivitis can occur in sexually active children and adolescents; the mode of transmission is similar to that of adults. Treatment may consist of ceftriaxone, 1 g IM plus saline irrigation. Alternatively, ceftriaxone 1 g IM or IV may be administered for 5 days along with saline irrigation.
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Occasionally a Neisseria conjunctivitis is attributable to N. meningitides. The eye may act as a portal and patients may develop meningococcemia and/or meningitis. These patients should be treated with ceftriaxone and their contacts given prophylaxis with Rifampin.
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Chlamydia Trachomatis
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Chlamydial eye infections can occur outside of the newborn period. Infection of children and adolescents may warrant an investigation for child sexual abuse and/or other concomitant sexually transmitted infections. Treatment consists of systemic oral erythromycin for 2 to 3 weeks. Children aged 1 and older may be treated with a single oral dose of azithromycin (20 mg/kg with a maximum dose of 1 g).7
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Allergic Conjunctivitis
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Seasonal and Perennial Allergic Conjunctivitis
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Itching is frequently the hallmark of allergic conjunctivitis. Seasonal allergic conjunctivitis has its onset of symptoms in either the fall or spring. Patients with sensitivity to grass have more symptoms in the spring, whereas individuals sensitive to ragweed have more symptoms in the fall. Patients often complain of bilateral itchy, watery eyes with a burning sensation. The conjunctiva is mildly inflamed with varying degrees of edema. Perennial allergic conjunctivitis is a variant with symptoms on a year-round basis and often allergens such as dust, mites, animal dander, and feathers are responsible for it. This conjunctivitis represents a type I hypersensitivity reaction.
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Treatment consists of a combination of topical vasoconstrictors (naphazoline-antazoline and naphazoline pheniramine), antihistamines (levocabastine 0.05%, emedastine difumarate 0.05%, epinastine, azelastine; usually used at one drop twice a day), topical steroids (rimexolone 1% or loteprednol etabonate 0.2%; one drop four times a day), and anti-inflammatory agents (ketorolac 0.5% or diclofenac 0.1%, one drop four times a day). Systemic anti-histamines such as loratadine may be of some benefit. Mast cell stabilizers (Cromolyn sodium 4%, nedocromil 2%, pemirolast potassium 0.1%, and lodoxamide tromethamine 0.1%) eye drops have also been shown to be effective when used as a prophylactic agent (Fig. 98-7). They should be used in conjunction with antihistamines as they do not relieve existing symptoms. Olopatadine and ketotifen (both one drop, twice a day) are both anti-histamines and mast cell stabilizers.
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Vernal Conjunctivitis
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Vernal keratoconjunctivitis is a rare condition mainly affecting children under the age of 10. It is common in warm, dry climates, and occurs most commonly in males (male-to-female ratio of 2:1). Often there is a significant history of atopy. Peak incidence is between April and August. Patients usually have a history of bilateral itching, foreign-body sensation, clear mucoid discharge, photophobia, and injection. The giant papillae involve the upper tarsal conjunctiva and consist of large “cobblestone” papillae. The patho-physiology is not entirely clear; IgE and IgG are thought to play a role. The mainstay of treatment consists of mast cell stabilizers and topical antihistamines. Systemic antihistamines, anti-inflammatory drops, and steroid drops may also be added. Cyclosporine drops are reserved for steroid-resistant disease.8
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Special Forms of Conjunctivitis
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Patients with Stevens–Johnson syndrome may have severe conjunctival involvement. In the acute phase of the disease, the palpebral and ocular conjunctiva can scar together. Often goblet cells are lost in the conjunctival epithelium and the mucous layer of tear film is lost. As mucus allows tear film to stick to the surface of the eye, the dry-eye state of Stevens–Johnson syndrome is characterized by abundant tears that do not cover the surface of the eye because they are unable to adhere to it. Treatment consists of a combination of topical lubricants and antibiotics.
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Kawasaki disease is associated with a bilateral bulbar, nonexudative conjunctivitis. This diagnosis should be suspected in patients who have fever for more than 5 days and have conjunctivitis, strawberry tongue, cervical adenopathy, fissuring of the lips, diffuse oral injection, erythema and induration of the hands and feet, rash, and desquamation of the fingers and toes. Not all symptoms are required to make the diagnosis.
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A chronic blepharoconjunctivitis can be caused by Phthirus pubis when the eyelashes are infected by nits or by the bug itself. The only recognized lice to infect the eyelashes are pubic lice. The type of conjunctivitis seen with lice results from a hypersensitivity reaction. Systemic treatment of the organism is necessary for successful eradication. Eye ointments have been used for treatment because they are thought to paralyze and smother the lice. A cotton-tip applicator should be used for debridement prior to the placement of the ointment.
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Molluscum contagiosum can cause conjunctivitis when the virus is shed into the eye. Typically, it causes a chronic conjunctivitis that does not respond to topical antimicrobials. The problem results from the virus protein, which is toxic to the eye. One may see lesions on the eyelids that are often buried between the eyelashes. Eradication of the virus requires that the lesions be opened with a needle and the central core of the umbilicated region be removed. Bleeding into the core is considered definitive treatment.
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Other viral syndromes can be associated with nonspecific conjunctivitis. These include rubella, influenza, mumps, measles, infectious mononucleosis, and cytomegalovirus. Papillomavirus can cause eyelid warts, which shed on the conjunctiva, causing a type of conjunctivitis similar to that described for molluscum contagiosum.
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Parinaud oculoglandular syndrome is a rare manifestation of cat scratch disease that occurs when the conjunctiva is directly inoculated with Bartonella henselae or Afipia felis. The condition manifests as a unilateral granulomatous or follicular conjunctivitis. Lymphadenopathy in the preauricular, cervical, and/or submandibular regions is common. Treatment consists of oral doxycycline, erythromycin, or ciprofloxacin. A similar syndrome can be caused by infections with Francisella tularensis, Sporothrix schenckii, Mycobacterium tuberculosis, or Treponema pallidum.
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Other systemic diseases presenting with eye findings mimicking conjunctivitis include ataxia-telangiectasia, where large tortuous vessels are noted on the bulbar conjunctiva. Patients with Lyme disease may develop nonspecific conjunctivitis with or without eye pain. There are many different causes of a red eye in children including conjunctivitis in its many forms as well as other local and systemic entities (Table 98-3).
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