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Pediatric uveitis
Pediatr Clin N Am 50 (2003) 125 – 136
Pediatric uveitis Hemang Patel, MD, Debra Goldstein, MD, FRCSC* Department of Ophthalmology and Visual Sciences, 1855 West Taylor Street, University of Illinois at Chicago, Chicago, IL 60612, USA
Definition of uveitis Uveitis is defined as an inflammation of the uveal tract, which encompasses the iris, ciliary body, and choroid. Although uveitis in the pediatric age group comprises only approximately 5% to 10% of all cases, its prompt diagnosis and management are vital in the preservation of vision [1]. To facilitate the understanding of this entity, it is important to be able to recognize the terminology.
Acute uveitis: inflammation that has a sudden onset and lasts for 6 weeks or less Anterior uveitis: inflammation of the iris or ciliary body or both Aqueous cell: presence of white or red blood cells or pigmented cells floating in the anterior chamber Aqueous flare: leakage of proteins into the aqueous from damaged blood vessels Band keratopathy: deposits of calcium in Bowman’s layer of the cornea seen in chronic iridocyclitis Busacca nodules: white or yellowish nodules found in the stroma of the iris (Fig. 1) Choroiditis: inflammation of the choroid Chorioretinitis: primary inflammation of the choroid with secondary inflammation of the retina Chronic uveitis: inflammation that persists for months to years; onset is insidious and often asymptomatic Ciliary flush: injection of circumcorneal blood vessels
* Corresponding author. E-mail address: [email protected] (D. Goldstein). 0031-3955/03/$ – see front matter D 2003, Elsevier Science (USA). All rights reserved. PII: S 0 0 3 1 - 3 9 5 5 ( 0 2 ) 0 0 1 0 6 - 2
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Cystoid macular edema: swelling of the inner layers of the macular retina which may result from intraocular inflammation and may lead to decreased vision Cyclitis: inflammation of the ciliary body Endophthalmitis: intraocular inflammation involving all layers of the eye but not extending past the sclera Floaters: moving lines or specks in the field of vision Hypopyon: a grossly visible layer of white blood cells in the anterior chamber; usually located inferiorly with a flat superior edge Hypotony: low intraocular pressure Iridocyclitis: primary inflammation of the iris with secondary inflammation of the ciliary body Iritis: inflammation of the iris Keratic precipitates (KP): collections of cells that form on the corneal endothelium (posterior cornea) (Fig. 2) Keratitis: inflammation of the cornea from infectious or inflammatory causes Koeppe nodules: whitish or yellowish nodules found on the pupillary margin of the iris (see Fig. 1) Leukocoria: white pupil Microphthalmia: small, internally disorganized eye Papillitis: optic nerve inflammation Phthisis bulbi: shrunken, disorganized, sightless eye Posterior uveitis: inflammation of the choroid Retinitis: inflammation of the retina Retinochoroiditis: inflammation of the retina with secondary inflammation of the choroid Periphlebitis: inflammation of the retinal blood vessels Synechia(e): fibrous adhesion of the iris to the peripheral cornea or lens Vitritis: inflammatory cells in the vitreous cavity
Clinical classification There are multiple methods of classifying uveitis as described in Table 1. Assigning a particular category aids in defining the proper diagnosis and then tailoring the management to that individual condition. In this article a combination of these methods is used.
Clinical features The presentation of a child with uveitis varies with the anatomic location of the inflammation. Although most of the signs and symptoms are classic, none are pathognomonic. It is also vital to realize that children do not always reveal their complaints, nor are young children able to verbalize their complaints as adults do.
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Fig. 1. Nodules at the pupillary border (Koeppe nodules) and on the iris stroma (Busacca nodules) in this patient with sarcoidosis. (See also Color Plate 9.)
Therefore it is the responsibility of the clinician to be able to elicit information from the parents and sometimes to act independently in the benefit of the child [1]. Acute anterior uveitis will frequently present with a sudden onset of photophobia, pain, redness, decreased vision, and tearing. These symptoms are less commonly seen with chronic anterior uveitis, which can result in a quietappearing eye with minimal symptoms, even though severe intraocular inflammation may be present. Some signs seen on examination include conjunctival and circumcorneal injection (ciliary flush), keratic precipitates, aqueous cells, aqueous flare, iris nodules (Koeppe and Busacca), iris atrophy, iris neovascularization, posterior synechiae, and anterior vitreous cells. In intermediate uveitis, the child predominantly complains of floaters that are persistent and nonclearing. In some patients, decreased central vision may also be a complaint. Vitritis and the absence of a focal inflammatory lesion in the fundus are generally the rule on examination. In some cases, there can be peripheral periphlebitis, a gray-white plaque in the inferior pars plans called snowbanking and small exudates in the vitreous called snowballs. Floaters and decreased vision are the two primary symptoms of posterior uveitis. Based on the location of the inflammatory lesion, the child may complain of one or both symptoms concurrently. Examination may reveal vitreous
Fig. 2. Large, greasy-looking, mutton-fat keratic precipitates in a patient with sarcoidosis. (See also Color Plate 10.)
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opacities, choroiditis, retinitis, periphlebitis, retinal neovascularization, retinal detachment, and pathology involving the optic nerve head (papillitis, edema, granuloma, and optic atrophy).
Anterior uveitis Idiopathic uveitis In approximately 29% to 50% of patients initially diagnosed with acute or chronic anterior uveitis, there is no systemic association [2]. These cases are termed idiopathic. In the remaining cases, a specific systemic diagnosis may be assigned. Trauma-related uveitis Trauma is a major cause of uveitis in children. Iritis can result from mild or severe blunt trauma to the globe or orbit. The patient will complain of photophobia, redness, and pain of the affected eye about 1 to 3 days after the injury. Clinically, there will be aqueous cells and flare with normal, low, or elevated intraocular pressure. Posterior inflammation can manifest in the forms of retinal edema, retinal detachment, vitreous opacities, and papillitis. In cases involving a projectile, an intraocular foreign body must be ruled out by ophthalmic and radiographic examination. HLA B27 – associated uveitis HLA B27 is a class I major histocompatibility antigen, which predisposes to several diseases including ankylosing spondylitis, reactive arthritis (Reiter’s syndrome), inflammatory bowel disease, and psoriasis. It also predisposes to uveitis, with or without one of the other conditions. HLA B27 uveitis comprises about 16% of cases of anterior uveitis in children [3]. Ankylosing spondylitis primarily affects older boys. It tends to manifest as lower extremity involvement in contrast to the lower back pain seen in adults. Ocular manifestations occur in 25% of patients with this disorder [4]. Bilateral involvement is seen in 80% of patients is but rarely simultaneous. Iritis is the most common manifestation, with recurrent attacks. Attacks can range in severity from mild to severe, with fibrin membrane or hypopyon formation in the anterior chamber. The triad of arthritis, urethritis, and conjunctivitis characterizes Reiter’s syndrome. Iritis occurs in 3% to 12% of these patients [4]. In children, these cases often follow a gram-negative dysentery. Psoriatic arthritis is seen in 20% of patients with psoriasis [4]. Joint involvement can be pauciarticular or polyarticular and usually involves the distal joints of the hands and feet as well as the sacroiliac joints. Uveitis occurs more frequently in girls than in boys and is of a chronic nature.
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Inflammatory bowel disease encompasses ulcerative colitis and Crohn’s disease, both of which may be associated with mild inflammation of large joints. Iridocyclitis occurs in 2% to 11% of these patients [3]. Ocular inflammation is thought to coincide with the gastrointestinal or joint inflammation. In some patients, colectomy has resulted in resolution of ocular inflammation. Patients with inflammatory bowel disease or any HLA-B27 disease are generally treated with topical steroids and cycloplegic agents. Severe attacks may require periocular depot injections of steroid or oral steroids. The iridocyclitis is often recurrent, with the first episode being most severe. Sarcoidosis-associated uveitis Sarcoidosis is a multisystem granulomatous disorder that can affect almost every organ in the body except the adrenal glands. There are two presenting age groups in the pediatric population. The group with onset of disease between ages of 8 and 15 years generally has pulmonary involvement with associated lymphadenopathy, hepatosplenomegaly, and ocular involvement. The other, group with onset of disease at less than age 5 years, has significantly less pulmonary involvement but can more commonly present with the triad of arthritis, skin rash, and uveitis [3]. Ocular manifestation is most commonly in the form of anterior uveitis. Most of these patients will have a chronic variety with the presence of keratic precipitates, iris nodules, and aqueous cells. These patients generally have minimal pain and photophobia. An acute form can also manifest, characterized by severe pain, redness, and photophobia. Treatment of anterior uveitis in most cases consists of topical corticosteroids and cycloplegics. Severe cases may require periocular or systemic steroids. Posterior segment inflammation with the development of vitritis and choroidal/optic nerve granulomas can also occur. Routine eye examinations are necessary in these patients because of the risk of development of inflammation-induced complications including cataract and glaucoma [4]. Herpes-associated uveitis Iridocyclitis can develop from either herpes simplex (HSV) or herpes zoster (HZV) infections. Uveitis related to herpes simplex usually is seen in association with disciform or stromal keratitis, although the cornea can be normal. There can be a moderate amount of aqueous cells with posterior synechiae, keratic precipitates, hyphema, and hypopyon. Anterior uveitis can also be seen in a systemic varicella zoster (chicken pox) infection or with herpes zoster ophthalmicus (HZO). Markedly elevated intraocular pressures, keratitis, hyphema, and hypopyon can accompany the iridocyclitis. Treatment of uveitis caused by either HSV or HZV may be with topical cycloplegics and steroids. Topical antiviral agents may be used to protect the cornea in cases of recurrent keratitis. Oral antiviral agents may be of benefit in treating the uveitis.
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Table 1 Categories of clinical classification Anatomic
Clinical
Etiologic
Anterior Intermediate Posterior Diffuse
Acute Chronic Recurrent
Infectious Immune/noninfectious Idiopathic
Juvenile rheumatoid arthritis – associated uveitis Juvenal rheumatoid arthritis, also called juvenile chronic arthritis or juvenile idiopathic arthritis, is the most common cause of anterior uveitis in the pediatric population. Juvenal rheumatoid arthritis affects 60,000 to 120,000 children in the United States each year [5]. Onset is most often between the ages of 2 and 4 years; the condition is more common in girls than boys in a 3:2 ratio. Juvenal rheumatoid arthritis-associated uveitis is seen in 20% of all patients diagnosed with this disease. Uveitis tends to develop after the development of arthritis [6]. Juvenal rheumatoid arthritis is a chronic synovitis that is characteristically divided into three major groups based on presentation: systemic, polyarticular, and pauciarticular [6]. Systemic juvenal rheumatoid arthritis (Still’s disease) is seen in children under age 5 years. It is characterized by a high fever with one of the following signs: lymphadenopathy, splenomegaly, hepatomegaly, pericarditis, or transient maculopapular rash on the trunk and limbs. Arthralgia or arthritis is typically minimal to absent at initial onset, and these patients rarely develop any ocular signs of inflammation [6]. Patients in the polyarticular group account for 40% of all cases of juvenal rheumatoid arthritis. Five or more joints are affected during the first 3 months; the knees are most commonly affected, followed by the wrists and ankles. These patients have a 7% to 14% incidence of developing uveitis [6]. The pauciarticular form of juvenal rheumatoid arthritis is seen in 40% of the affected patients. Four joints or fewer are affected, with the knees being the joint most commonly involved. Uveitis is most prevalent in this group, with a 78% to 91% incidence [6]. Girls in this group who are antinuclear antibody (ANA)– positive and Rhesus factor (RH) –negative are at the highest risk for the development of uveitis [4].
Table 2 Screening protocol for patients with juvenile rheumatoid arthritis: low-risk patients Disease type/onset Screening interval
Systemic onset ANA-negative or Any onset with joint disease > 7 years and no eye disease Yearly
Abbreviation: ANA, antinuclear antibody
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Table 3 Screening protocol for patients with juvenile rheumatoid arthritis: moderate-risk patients Disease type
Pauci or polyarticular
Disease characteristics
ANA-positive, onset of joint disease < 7 years, disease duration of 5 years or ANA-negative, disease duration of < 5 years or ANA positive, disease onset > 7 years, disease duration 5 years Every 6 months
Screening interval
Abbreviation: ANA, antinuclear antibody
The mean age of onset of uveitis varies from 6 to 13 years. Ninety percent of the children with juvenal rheumatoid arthritis who develop uveitis do so within 7 years of the onset of arthritis, with girls predating boys by about 4 years [4– 6]. Uveitis in these children is generally asymptomatic and chronic. Even with the presence of severe aqueous cells, these children rarely have symptoms and present with white, quiet-appearing eyes [5]. Positive prognosticators of final visual outcome include good visual acuity at presentation, male sex, and older age at disease onset. Prolonged, uncontrolled inflammation leads to multiple sight-impeding complications, of which cataracts and band keratopathy are the most prevalent. Glaucoma is common and may result in visual loss. The development of hypotony portends a poor outcome. Topical corticosteroids and mydriatic agents remain the initial treatment of choice. Periocular and oral corticosteroids may be added for further control of inflammation. Oral nonsteroidal anti-inflammatory drugs (NSAIDs) have been found to be a useful adjunct in tapering steroids in many patients. Systemic methotrexate is a good choice for a steroid-sparing agent in patients not responding to NSAIDS. Oral azathioprine and cyclosporine may also be used. There are few data on the use of tumor necrosis factor (TNF) inhibitors in juvenal rheumatoid arthritis– related uveitis [3,5,7]. The silent nature of this disease necessitates a strict ophthalmic follow-up regimen for all juvenal rheumatoid arthritis patients. Risk-stratified schedules are presented in Tables 2 –4.
Intermediate uveitis Intermediate uveitis is an ocular inflammation involving primarily the vitreous and peripheral retina. Intermediate uveitis accounts for approximately 25% of all Table 4 Screening protocol for patients with juvenile rheumatoid arthritis: high-risk patients Disease type
Pauci or polyarticular
Disease characteristics
ANA-positive and disease onset < 7 years and disease duration < 5 years Every 3 to 4 months
Screening interval Abbreviation: ANA, antinuclear antitody
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pediatric uveitis. The disease has no racial or sexual predilection and is bilateral but asymmetric in 80% of cases [3]. Although its etiology has not yet been determined, different mechanisms have been proposed. Associations have also been made to the demyelinating disorder multiple sclerosis and immune processes such as sarcoidosis and Lyme disease. Symptoms generally consist of floaters or decreased vision. Because there is minimal involvement of the anterior chamber, pain and photophobia are uncommon, although young children may present with more significant anterior chamber reaction and pain. On examination, inflammatory cells and snowball vitreous opacities are seen. In a subgroup called pars planitis, an exudate or snowbank may be seen inferiorly over the area of the pars plans and ora serrata. Intermediate uveitis may follow one of three clinical courses: self-limited, chronic indolent, or severe with complications. Complications include band keratopathy, glaucoma, retinal detachment, vitreous hemorrhage, optic disc edema, cystoid macular edema, and cataracts; the last two are the most common cause of secondary visual loss [7]. Treatment of this entity is generally reserved for patients whose visual acuity has declined to a level worse than 20/40, those who show evidence of cystoid macular edema, or those with significant vitreous inflammation. The mainstay of treatment is either periocular or systemic steroids. Topical steroids are of little or no benefit. If corticosteroids cannot adequately control the inflammation, steroid-sparing agents such as methotrexate or cyclosporine may also be used [8]. Ultimate visual prognosis seems to be related more to the severity of the disease than the chronicity.
Posterior uveitis Toxoplasmosis-associated uveitis Toxoplasmosis is a parasitic disease caused by the intracellular protozoan Toxoplasma gondii. Cats are the definitive host for this organism. Ingestion of the cyst form (bradyzoite) in undercooked meat is the major source of infection in humans; it may also be contracted through contact with cat feces [9]. Because the organism can cross the placenta, pregnant women should avoid contact with cat litter boxes. The organism has a predilection for cardiac, muscular, and neural tissue, including retina. Congenital systemic toxoplasmosis occurs in 1 out of every 10,000 births and presents in one of three forms. The first form is inactive at birth and is not recognized until later inflammation is seen. A second type is active at birth and is recognized by the three C’s: convulsions, intracranial calcifications, and chorioretinitis or retinochoroiditis, the last being bilateral in 85% of the patients. The last type is a recurrent form that parallels the acquired form. There are five types of acquired toxoplasmosis: exanthematous, meningoencephalitic, lymphadenopathic, influenzal, and ocular.
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Ocular toxoplasmosis can present as papillitis, retinitis, and iridocyclitis. It is the most common type of childhood posterior uveitis, accounting for up to 50% of cases. Patients present with complaints of floaters or decreased vision. On examination, a yellowish-white, raised lesion is seen in the retina and represents a focal area of infectious retinitis with underlying choroidal inflammation (retinochoroiditis). As these lesions heal, they leave areas of atrophy with pigmentation around the edges (chorioretinal scar). It is often difficult to determine if ocular disease is congenital or acquired. Bilateral macular scars usually represent congenital disease. Active, white retinitis in the absence of a scar usually represents acquired disease. An active form of retinitis adjacent to an old scar may represent either congenital or acquired disease. Toxoplasmic ocular inflammatory disease can run a course of up to 6 months before inactivation and the initiation of healing, although it usually runs its course within 2 to 3 months. Recurrence is often accompanied with a severe anterior uveitis with the presence of iris nodules, posterior synechiae, and marked aqueous cells. Examination of these patients will reveal satellite lesions adjacent to old chorioretinal scars. In immunocompetent patients, ocular toxoplasmosis is self-limited. Treatment is indicated, however, for lesions in the macula, near the optic nerve, or those associated with severe vitritis. Quadruple therapy including sulfadiazine, pyramethamine, clindamycin, and folinic acid are now recommended (see Table 2 for recommended doses). Prednisone may be added when the macula is threatened. Recently azithromycin and atovaquone have been proposed as monotherapies. With either regimen, antimicrobial treatment is indicated for 4 to 5 weeks. Overall visual prognosis is dependent on the patient’s immune status, location of the lesion, and the hardiness of the organism.
Ocular toxocariasis The dog roundworm Toxocara canis is another cause of infectious pediatric posterior uveitis. The canine intestinal parasite is found in up to 50% of healthy dogs [3]. Humans are infected after ingestion of ova-contaminated soil or vegetables. Whereas the parasite’s life cycle is completed in dogs, it is halted in humans. In humans, the eggs mature into larvae in the small intestine, pass through the intestinal walls into blood vessels, and then to liver and lungs from which they reach other organs including the eye. Systemic infection is called visceral larva migrans (VLM) and is usually asymptomatic; however, some patients may suffer from fever, cough, malaise, anorexia, or seizures. Ocular involvement is usually unilateral, can occur concurrently with VLM or several years later, and can take one of three forms: posterior pole granuloma, peripheral granuloma, or endophthalmitis. The posterior pole granuloma is the most common form seen in children. The age of presentation is between 6 and 14 years. The eye is generally quiet externally; there may be leukocoria and strabismus. On examination, a solitary,
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white, elevated mass is seen in the macula or near the optic nerve. The only presenting complaint may be decreased vision. Peripheral granulomas tend to present at an older age. Like the posterior granuloma, the eye is usually white and quiet externally. In this case, an elevated, whitish lesion is usually seen in the peripheral retina and can be associated with tractional bands on the retina, which can lead to macular heterotropia, strabismus, and decreased vision. Endophthalmitis is more commonly seen in patients aged 2 to 9 years. There is marked visual decline and moderate to severe vitritis. On examination, signs of anterior uveitis are present including aqueous cells and flare, keratic precipitates, posterior synechiae, and hypopyon. On fundus examination, retinal detachment may be visualized. This condition must be considered in the differential diagnosis of any pediatric patient with leukocoria. Adjuncts for diagnosis include aqueous cytology and antibody testing. Eosinophils in the aqueous and the presence of any antibody titer (undiluted serum) may have significance. Peripheral granulomas with minimal inflammation generally require observation only, not treatment. For posterior granulomas and endophthalmitis, periocular or systemic corticosteroids should be administered. There is no agreed convention on the use of antihelminthics such as thiobendazole. It is agreed, however, that they must be used in conjunction with steroids because of the exuberant inflammatory reaction following the death of the parasite. Overall, the prognosis for visual acuity is poor with a posterior granuloma or endophthalmitis. Cutaneous larva migrans is caused by a different organism and does not cause uveitis. Rubella-associated uveitis Rubella or German measles usually starts as a viral prodrome of malaise and fever that evolves into a maculopapular rash originating on the trunk and spreading to the extremities. Ocular involvement can take place in both acquired and congenital forms. The incidence of eye findings in the acquired disease is 25% to 50% and takes the form of conjunctivitis, iritis, and, rarely, a bilateral retinitis [3]. Other signs include cataract, glaucoma, aqueous cells, iris atrophy, and posterior synechiae. The retina of patients with congenital rubella is characterized by the classic saltand-pepper fundus along with normal-appearing blood vessels and an occasional pale optic nerve. Despite these retinal changes, vision is usually not affected. Glaucoma and keratitis may also be seen in patients with this condition and may affect vision. These ocular findings make up a part of the congenital rubella syndrome, which incorporates systemic findings such as heart defects, sensorineural hearing loss, mental and growth retardation, and hepatosplenomegaly. A summary of ocular findings associated with TORCHS syndromes may be found in Table 5.
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Table 5 Ocular findings associated with TORCHS syndromes Iritis Toxoplasmosis Rubella Cmv Herpes Syphilis a b c
Yes Yes No Yes Yes
Keratitis No Yes No Yes Yes
Cataract No Yes Yes No No
Glaucoma No Yes No Yesc Yes
Retinitis a
Yes Yesb Yesb Yes Yesb
Small eye No Yes Yes Yes Yes
macular or peripheral scars ‘‘salt and pepper’’ appearance when associated with iritis or iridocyclitis
Syphilis-associated uveitis Ocular involvement can be seen with either acquired or congenital forms of syphilis. In the congenital form, Treponema pallidum organisms can pass from placenta to the fetus. In addition to the eyes, syphilis can affect bone, bone marrow, central nervous system, liver, lungs, and spleen. Fundus examination may reveal a saltand-pepper or bone spicule chorioretinitis, along with pallor of the optic nerve. Iritis and interstitial keratitis may also be seen, the latter being incorporated into the so-called Hutchinson’s triad, which adds deafness and malformed incisors (known as Hutchinson’s teeth) [4]. In the acquired form, inflammation can be anterior or posterior. Posterior involvement can be in the form of vitritis, chorioretinitis, vasculitis, optic papillitis, or optic atrophy [4]. Syphilis-associated inflammation does not respond well to corticosteroids. Treatment varies with the stage of the disease; however, the criterion standard for treatment is 10 days of intravenous penicillin for congenital or neurosyphilis. Masquerade syndromes Conditions that mimic uveitis are known as masquerade syndromes. Although they may not be primarily infectious or inflammatory, their importance to the overall well being of the patient cannot be overlooked. These conditions must be considered in the differential diagnosis of ocular inflammation. Retinoblastoma Retinoblastoma is the most common malignant pediatric ocular tumor. It must be ruled out in any case of intraocular inflammation in a patient less than 5 years old. In retinoblastoma, both anterior and posterior segment inflammation may also be present. Occasionally, the retinoblastoma patient may present with a red, painful eye. On gross examination, one may even be able to see a pseudohypopyon which represents a layering of tumor cells in the anterior chamber. With exophytic tumors an endophthalmitic picture may be seen. These patients should be urgently referred to an ophthalmologist for a complete work up.
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Leukemia Ocular inflammation is seen in patients with acute lymphoblastic, acute myelogenous, and acute monocytic leukemia. The anterior segment findings include heterochromia, iris infiltrates, spontaneous hyphema, leukemic cells in the aqueous, or pseudohypopyon. Retinal involvement usually appears as dilated retinal vessels and retinal hemorrhages, some of which have white centers consisting of leukemic cells. Choroidal involvement, rarely detected clinically, is represented by leukemic infiltration. Optic nerve and orbital involvement are also seen fairly commonly. Juvenile xanthogranuloma Juvenile xanthogranuloma is a non-neoplastic histiocytic proliferation that usually develops in children under the age of 2 years. Children with juvenile xanthogranuloma can present with anterior chamber cell or spontaneous hyphema. There also may be iris heterochromia from the presence of fleshy, yellow-brown iris masses that can be localized or diffusely infiltrative. Skin examination may reveal one or more round, orange/tan papules. This condition is generally self-limited and will usually regress by age 5 years.
Summary Uveitis in children is an entity most pediatricians and ophthalmologists seldom encounter. It is prevalent in society, however, and the high incidence of sight-threatening complications in untreated children warrants a baseline knowledge of the diseases and disorders involved as well as a sense of when to refer to a specialist.
References [1] Tugal-Tutkun I, Havrlikova K, Power WJ, et al. Changing patterns in uveitis of childhood. Ophthalmology 1996;6:293 – 8. [2] Pivetti-Pezzi P. Uveitis in children. Eur J Ophthalmol 1996;6:293 – 8. [3] Forster DJ, Rao NA. Uveitis in children. In: Wright KM, editor. Pediatric ophthalmology and strabismus. New York: Mosby-Year Book; 1995. [4] Nussenblatt RB, Whitcup SM, Palestine AG. Uveitis. New York: Mosby; 1996. [5] Kanski J. Juvenile arthritis and uveitis. Surv Ophthalmol 1990;34(4):253 – 67. [6] Dana MR, Merayo-Lloves J, Schaumberg DA, et al. Visual outcomes prognosticators in juvenile rheumatoid arthritis-associated uveitis. Ophthalmology 1997;104(2):236 – 44. [7] Giles C. Uveitis in childhood. Ann Ophthalmol 1989;21:13 – 28. [8] Kilmartin DJ, Forrester JV, Dick AD. Cyclosporin A therapy in refractory non-infectious childhood uveitis. Br J Ophthalmol 1998;82(7):732 – 42. [9] Mets MB, Holfels E, Boyer KM, et al. Manifestations of congenital toxoplasmosis. Am J Ophthalmol 1996;122:309 – 24. [10] Kanski J. Uveitis. Butterworth and Company; 1987.
Pediatric uveitis Hemang Patel, MD, Debra Goldstein, MD, FRCSC* Department of Ophthalmology and Visual Sciences, 1855 West Taylor Street, University of Illinois at Chicago, Chicago, IL 60612, USA
Definition of uveitis Uveitis is defined as an inflammation of the uveal tract, which encompasses the iris, ciliary body, and choroid. Although uveitis in the pediatric age group comprises only approximately 5% to 10% of all cases, its prompt diagnosis and management are vital in the preservation of vision [1]. To facilitate the understanding of this entity, it is important to be able to recognize the terminology.
Acute uveitis: inflammation that has a sudden onset and lasts for 6 weeks or less Anterior uveitis: inflammation of the iris or ciliary body or both Aqueous cell: presence of white or red blood cells or pigmented cells floating in the anterior chamber Aqueous flare: leakage of proteins into the aqueous from damaged blood vessels Band keratopathy: deposits of calcium in Bowman’s layer of the cornea seen in chronic iridocyclitis Busacca nodules: white or yellowish nodules found in the stroma of the iris (Fig. 1) Choroiditis: inflammation of the choroid Chorioretinitis: primary inflammation of the choroid with secondary inflammation of the retina Chronic uveitis: inflammation that persists for months to years; onset is insidious and often asymptomatic Ciliary flush: injection of circumcorneal blood vessels
* Corresponding author. E-mail address: [email protected] (D. Goldstein). 0031-3955/03/$ – see front matter D 2003, Elsevier Science (USA). All rights reserved. PII: S 0 0 3 1 - 3 9 5 5 ( 0 2 ) 0 0 1 0 6 - 2
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Cystoid macular edema: swelling of the inner layers of the macular retina which may result from intraocular inflammation and may lead to decreased vision Cyclitis: inflammation of the ciliary body Endophthalmitis: intraocular inflammation involving all layers of the eye but not extending past the sclera Floaters: moving lines or specks in the field of vision Hypopyon: a grossly visible layer of white blood cells in the anterior chamber; usually located inferiorly with a flat superior edge Hypotony: low intraocular pressure Iridocyclitis: primary inflammation of the iris with secondary inflammation of the ciliary body Iritis: inflammation of the iris Keratic precipitates (KP): collections of cells that form on the corneal endothelium (posterior cornea) (Fig. 2) Keratitis: inflammation of the cornea from infectious or inflammatory causes Koeppe nodules: whitish or yellowish nodules found on the pupillary margin of the iris (see Fig. 1) Leukocoria: white pupil Microphthalmia: small, internally disorganized eye Papillitis: optic nerve inflammation Phthisis bulbi: shrunken, disorganized, sightless eye Posterior uveitis: inflammation of the choroid Retinitis: inflammation of the retina Retinochoroiditis: inflammation of the retina with secondary inflammation of the choroid Periphlebitis: inflammation of the retinal blood vessels Synechia(e): fibrous adhesion of the iris to the peripheral cornea or lens Vitritis: inflammatory cells in the vitreous cavity
Clinical classification There are multiple methods of classifying uveitis as described in Table 1. Assigning a particular category aids in defining the proper diagnosis and then tailoring the management to that individual condition. In this article a combination of these methods is used.
Clinical features The presentation of a child with uveitis varies with the anatomic location of the inflammation. Although most of the signs and symptoms are classic, none are pathognomonic. It is also vital to realize that children do not always reveal their complaints, nor are young children able to verbalize their complaints as adults do.
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Fig. 1. Nodules at the pupillary border (Koeppe nodules) and on the iris stroma (Busacca nodules) in this patient with sarcoidosis. (See also Color Plate 9.)
Therefore it is the responsibility of the clinician to be able to elicit information from the parents and sometimes to act independently in the benefit of the child [1]. Acute anterior uveitis will frequently present with a sudden onset of photophobia, pain, redness, decreased vision, and tearing. These symptoms are less commonly seen with chronic anterior uveitis, which can result in a quietappearing eye with minimal symptoms, even though severe intraocular inflammation may be present. Some signs seen on examination include conjunctival and circumcorneal injection (ciliary flush), keratic precipitates, aqueous cells, aqueous flare, iris nodules (Koeppe and Busacca), iris atrophy, iris neovascularization, posterior synechiae, and anterior vitreous cells. In intermediate uveitis, the child predominantly complains of floaters that are persistent and nonclearing. In some patients, decreased central vision may also be a complaint. Vitritis and the absence of a focal inflammatory lesion in the fundus are generally the rule on examination. In some cases, there can be peripheral periphlebitis, a gray-white plaque in the inferior pars plans called snowbanking and small exudates in the vitreous called snowballs. Floaters and decreased vision are the two primary symptoms of posterior uveitis. Based on the location of the inflammatory lesion, the child may complain of one or both symptoms concurrently. Examination may reveal vitreous
Fig. 2. Large, greasy-looking, mutton-fat keratic precipitates in a patient with sarcoidosis. (See also Color Plate 10.)
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opacities, choroiditis, retinitis, periphlebitis, retinal neovascularization, retinal detachment, and pathology involving the optic nerve head (papillitis, edema, granuloma, and optic atrophy).
Anterior uveitis Idiopathic uveitis In approximately 29% to 50% of patients initially diagnosed with acute or chronic anterior uveitis, there is no systemic association [2]. These cases are termed idiopathic. In the remaining cases, a specific systemic diagnosis may be assigned. Trauma-related uveitis Trauma is a major cause of uveitis in children. Iritis can result from mild or severe blunt trauma to the globe or orbit. The patient will complain of photophobia, redness, and pain of the affected eye about 1 to 3 days after the injury. Clinically, there will be aqueous cells and flare with normal, low, or elevated intraocular pressure. Posterior inflammation can manifest in the forms of retinal edema, retinal detachment, vitreous opacities, and papillitis. In cases involving a projectile, an intraocular foreign body must be ruled out by ophthalmic and radiographic examination. HLA B27 – associated uveitis HLA B27 is a class I major histocompatibility antigen, which predisposes to several diseases including ankylosing spondylitis, reactive arthritis (Reiter’s syndrome), inflammatory bowel disease, and psoriasis. It also predisposes to uveitis, with or without one of the other conditions. HLA B27 uveitis comprises about 16% of cases of anterior uveitis in children [3]. Ankylosing spondylitis primarily affects older boys. It tends to manifest as lower extremity involvement in contrast to the lower back pain seen in adults. Ocular manifestations occur in 25% of patients with this disorder [4]. Bilateral involvement is seen in 80% of patients is but rarely simultaneous. Iritis is the most common manifestation, with recurrent attacks. Attacks can range in severity from mild to severe, with fibrin membrane or hypopyon formation in the anterior chamber. The triad of arthritis, urethritis, and conjunctivitis characterizes Reiter’s syndrome. Iritis occurs in 3% to 12% of these patients [4]. In children, these cases often follow a gram-negative dysentery. Psoriatic arthritis is seen in 20% of patients with psoriasis [4]. Joint involvement can be pauciarticular or polyarticular and usually involves the distal joints of the hands and feet as well as the sacroiliac joints. Uveitis occurs more frequently in girls than in boys and is of a chronic nature.
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Inflammatory bowel disease encompasses ulcerative colitis and Crohn’s disease, both of which may be associated with mild inflammation of large joints. Iridocyclitis occurs in 2% to 11% of these patients [3]. Ocular inflammation is thought to coincide with the gastrointestinal or joint inflammation. In some patients, colectomy has resulted in resolution of ocular inflammation. Patients with inflammatory bowel disease or any HLA-B27 disease are generally treated with topical steroids and cycloplegic agents. Severe attacks may require periocular depot injections of steroid or oral steroids. The iridocyclitis is often recurrent, with the first episode being most severe. Sarcoidosis-associated uveitis Sarcoidosis is a multisystem granulomatous disorder that can affect almost every organ in the body except the adrenal glands. There are two presenting age groups in the pediatric population. The group with onset of disease between ages of 8 and 15 years generally has pulmonary involvement with associated lymphadenopathy, hepatosplenomegaly, and ocular involvement. The other, group with onset of disease at less than age 5 years, has significantly less pulmonary involvement but can more commonly present with the triad of arthritis, skin rash, and uveitis [3]. Ocular manifestation is most commonly in the form of anterior uveitis. Most of these patients will have a chronic variety with the presence of keratic precipitates, iris nodules, and aqueous cells. These patients generally have minimal pain and photophobia. An acute form can also manifest, characterized by severe pain, redness, and photophobia. Treatment of anterior uveitis in most cases consists of topical corticosteroids and cycloplegics. Severe cases may require periocular or systemic steroids. Posterior segment inflammation with the development of vitritis and choroidal/optic nerve granulomas can also occur. Routine eye examinations are necessary in these patients because of the risk of development of inflammation-induced complications including cataract and glaucoma [4]. Herpes-associated uveitis Iridocyclitis can develop from either herpes simplex (HSV) or herpes zoster (HZV) infections. Uveitis related to herpes simplex usually is seen in association with disciform or stromal keratitis, although the cornea can be normal. There can be a moderate amount of aqueous cells with posterior synechiae, keratic precipitates, hyphema, and hypopyon. Anterior uveitis can also be seen in a systemic varicella zoster (chicken pox) infection or with herpes zoster ophthalmicus (HZO). Markedly elevated intraocular pressures, keratitis, hyphema, and hypopyon can accompany the iridocyclitis. Treatment of uveitis caused by either HSV or HZV may be with topical cycloplegics and steroids. Topical antiviral agents may be used to protect the cornea in cases of recurrent keratitis. Oral antiviral agents may be of benefit in treating the uveitis.
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Table 1 Categories of clinical classification Anatomic
Clinical
Etiologic
Anterior Intermediate Posterior Diffuse
Acute Chronic Recurrent
Infectious Immune/noninfectious Idiopathic
Juvenile rheumatoid arthritis – associated uveitis Juvenal rheumatoid arthritis, also called juvenile chronic arthritis or juvenile idiopathic arthritis, is the most common cause of anterior uveitis in the pediatric population. Juvenal rheumatoid arthritis affects 60,000 to 120,000 children in the United States each year [5]. Onset is most often between the ages of 2 and 4 years; the condition is more common in girls than boys in a 3:2 ratio. Juvenal rheumatoid arthritis-associated uveitis is seen in 20% of all patients diagnosed with this disease. Uveitis tends to develop after the development of arthritis [6]. Juvenal rheumatoid arthritis is a chronic synovitis that is characteristically divided into three major groups based on presentation: systemic, polyarticular, and pauciarticular [6]. Systemic juvenal rheumatoid arthritis (Still’s disease) is seen in children under age 5 years. It is characterized by a high fever with one of the following signs: lymphadenopathy, splenomegaly, hepatomegaly, pericarditis, or transient maculopapular rash on the trunk and limbs. Arthralgia or arthritis is typically minimal to absent at initial onset, and these patients rarely develop any ocular signs of inflammation [6]. Patients in the polyarticular group account for 40% of all cases of juvenal rheumatoid arthritis. Five or more joints are affected during the first 3 months; the knees are most commonly affected, followed by the wrists and ankles. These patients have a 7% to 14% incidence of developing uveitis [6]. The pauciarticular form of juvenal rheumatoid arthritis is seen in 40% of the affected patients. Four joints or fewer are affected, with the knees being the joint most commonly involved. Uveitis is most prevalent in this group, with a 78% to 91% incidence [6]. Girls in this group who are antinuclear antibody (ANA)– positive and Rhesus factor (RH) –negative are at the highest risk for the development of uveitis [4].
Table 2 Screening protocol for patients with juvenile rheumatoid arthritis: low-risk patients Disease type/onset Screening interval
Systemic onset ANA-negative or Any onset with joint disease > 7 years and no eye disease Yearly
Abbreviation: ANA, antinuclear antibody
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Table 3 Screening protocol for patients with juvenile rheumatoid arthritis: moderate-risk patients Disease type
Pauci or polyarticular
Disease characteristics
ANA-positive, onset of joint disease < 7 years, disease duration of 5 years or ANA-negative, disease duration of < 5 years or ANA positive, disease onset > 7 years, disease duration 5 years Every 6 months
Screening interval
Abbreviation: ANA, antinuclear antibody
The mean age of onset of uveitis varies from 6 to 13 years. Ninety percent of the children with juvenal rheumatoid arthritis who develop uveitis do so within 7 years of the onset of arthritis, with girls predating boys by about 4 years [4– 6]. Uveitis in these children is generally asymptomatic and chronic. Even with the presence of severe aqueous cells, these children rarely have symptoms and present with white, quiet-appearing eyes [5]. Positive prognosticators of final visual outcome include good visual acuity at presentation, male sex, and older age at disease onset. Prolonged, uncontrolled inflammation leads to multiple sight-impeding complications, of which cataracts and band keratopathy are the most prevalent. Glaucoma is common and may result in visual loss. The development of hypotony portends a poor outcome. Topical corticosteroids and mydriatic agents remain the initial treatment of choice. Periocular and oral corticosteroids may be added for further control of inflammation. Oral nonsteroidal anti-inflammatory drugs (NSAIDs) have been found to be a useful adjunct in tapering steroids in many patients. Systemic methotrexate is a good choice for a steroid-sparing agent in patients not responding to NSAIDS. Oral azathioprine and cyclosporine may also be used. There are few data on the use of tumor necrosis factor (TNF) inhibitors in juvenal rheumatoid arthritis– related uveitis [3,5,7]. The silent nature of this disease necessitates a strict ophthalmic follow-up regimen for all juvenal rheumatoid arthritis patients. Risk-stratified schedules are presented in Tables 2 –4.
Intermediate uveitis Intermediate uveitis is an ocular inflammation involving primarily the vitreous and peripheral retina. Intermediate uveitis accounts for approximately 25% of all Table 4 Screening protocol for patients with juvenile rheumatoid arthritis: high-risk patients Disease type
Pauci or polyarticular
Disease characteristics
ANA-positive and disease onset < 7 years and disease duration < 5 years Every 3 to 4 months
Screening interval Abbreviation: ANA, antinuclear antitody
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pediatric uveitis. The disease has no racial or sexual predilection and is bilateral but asymmetric in 80% of cases [3]. Although its etiology has not yet been determined, different mechanisms have been proposed. Associations have also been made to the demyelinating disorder multiple sclerosis and immune processes such as sarcoidosis and Lyme disease. Symptoms generally consist of floaters or decreased vision. Because there is minimal involvement of the anterior chamber, pain and photophobia are uncommon, although young children may present with more significant anterior chamber reaction and pain. On examination, inflammatory cells and snowball vitreous opacities are seen. In a subgroup called pars planitis, an exudate or snowbank may be seen inferiorly over the area of the pars plans and ora serrata. Intermediate uveitis may follow one of three clinical courses: self-limited, chronic indolent, or severe with complications. Complications include band keratopathy, glaucoma, retinal detachment, vitreous hemorrhage, optic disc edema, cystoid macular edema, and cataracts; the last two are the most common cause of secondary visual loss [7]. Treatment of this entity is generally reserved for patients whose visual acuity has declined to a level worse than 20/40, those who show evidence of cystoid macular edema, or those with significant vitreous inflammation. The mainstay of treatment is either periocular or systemic steroids. Topical steroids are of little or no benefit. If corticosteroids cannot adequately control the inflammation, steroid-sparing agents such as methotrexate or cyclosporine may also be used [8]. Ultimate visual prognosis seems to be related more to the severity of the disease than the chronicity.
Posterior uveitis Toxoplasmosis-associated uveitis Toxoplasmosis is a parasitic disease caused by the intracellular protozoan Toxoplasma gondii. Cats are the definitive host for this organism. Ingestion of the cyst form (bradyzoite) in undercooked meat is the major source of infection in humans; it may also be contracted through contact with cat feces [9]. Because the organism can cross the placenta, pregnant women should avoid contact with cat litter boxes. The organism has a predilection for cardiac, muscular, and neural tissue, including retina. Congenital systemic toxoplasmosis occurs in 1 out of every 10,000 births and presents in one of three forms. The first form is inactive at birth and is not recognized until later inflammation is seen. A second type is active at birth and is recognized by the three C’s: convulsions, intracranial calcifications, and chorioretinitis or retinochoroiditis, the last being bilateral in 85% of the patients. The last type is a recurrent form that parallels the acquired form. There are five types of acquired toxoplasmosis: exanthematous, meningoencephalitic, lymphadenopathic, influenzal, and ocular.
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Ocular toxoplasmosis can present as papillitis, retinitis, and iridocyclitis. It is the most common type of childhood posterior uveitis, accounting for up to 50% of cases. Patients present with complaints of floaters or decreased vision. On examination, a yellowish-white, raised lesion is seen in the retina and represents a focal area of infectious retinitis with underlying choroidal inflammation (retinochoroiditis). As these lesions heal, they leave areas of atrophy with pigmentation around the edges (chorioretinal scar). It is often difficult to determine if ocular disease is congenital or acquired. Bilateral macular scars usually represent congenital disease. Active, white retinitis in the absence of a scar usually represents acquired disease. An active form of retinitis adjacent to an old scar may represent either congenital or acquired disease. Toxoplasmic ocular inflammatory disease can run a course of up to 6 months before inactivation and the initiation of healing, although it usually runs its course within 2 to 3 months. Recurrence is often accompanied with a severe anterior uveitis with the presence of iris nodules, posterior synechiae, and marked aqueous cells. Examination of these patients will reveal satellite lesions adjacent to old chorioretinal scars. In immunocompetent patients, ocular toxoplasmosis is self-limited. Treatment is indicated, however, for lesions in the macula, near the optic nerve, or those associated with severe vitritis. Quadruple therapy including sulfadiazine, pyramethamine, clindamycin, and folinic acid are now recommended (see Table 2 for recommended doses). Prednisone may be added when the macula is threatened. Recently azithromycin and atovaquone have been proposed as monotherapies. With either regimen, antimicrobial treatment is indicated for 4 to 5 weeks. Overall visual prognosis is dependent on the patient’s immune status, location of the lesion, and the hardiness of the organism.
Ocular toxocariasis The dog roundworm Toxocara canis is another cause of infectious pediatric posterior uveitis. The canine intestinal parasite is found in up to 50% of healthy dogs [3]. Humans are infected after ingestion of ova-contaminated soil or vegetables. Whereas the parasite’s life cycle is completed in dogs, it is halted in humans. In humans, the eggs mature into larvae in the small intestine, pass through the intestinal walls into blood vessels, and then to liver and lungs from which they reach other organs including the eye. Systemic infection is called visceral larva migrans (VLM) and is usually asymptomatic; however, some patients may suffer from fever, cough, malaise, anorexia, or seizures. Ocular involvement is usually unilateral, can occur concurrently with VLM or several years later, and can take one of three forms: posterior pole granuloma, peripheral granuloma, or endophthalmitis. The posterior pole granuloma is the most common form seen in children. The age of presentation is between 6 and 14 years. The eye is generally quiet externally; there may be leukocoria and strabismus. On examination, a solitary,
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white, elevated mass is seen in the macula or near the optic nerve. The only presenting complaint may be decreased vision. Peripheral granulomas tend to present at an older age. Like the posterior granuloma, the eye is usually white and quiet externally. In this case, an elevated, whitish lesion is usually seen in the peripheral retina and can be associated with tractional bands on the retina, which can lead to macular heterotropia, strabismus, and decreased vision. Endophthalmitis is more commonly seen in patients aged 2 to 9 years. There is marked visual decline and moderate to severe vitritis. On examination, signs of anterior uveitis are present including aqueous cells and flare, keratic precipitates, posterior synechiae, and hypopyon. On fundus examination, retinal detachment may be visualized. This condition must be considered in the differential diagnosis of any pediatric patient with leukocoria. Adjuncts for diagnosis include aqueous cytology and antibody testing. Eosinophils in the aqueous and the presence of any antibody titer (undiluted serum) may have significance. Peripheral granulomas with minimal inflammation generally require observation only, not treatment. For posterior granulomas and endophthalmitis, periocular or systemic corticosteroids should be administered. There is no agreed convention on the use of antihelminthics such as thiobendazole. It is agreed, however, that they must be used in conjunction with steroids because of the exuberant inflammatory reaction following the death of the parasite. Overall, the prognosis for visual acuity is poor with a posterior granuloma or endophthalmitis. Cutaneous larva migrans is caused by a different organism and does not cause uveitis. Rubella-associated uveitis Rubella or German measles usually starts as a viral prodrome of malaise and fever that evolves into a maculopapular rash originating on the trunk and spreading to the extremities. Ocular involvement can take place in both acquired and congenital forms. The incidence of eye findings in the acquired disease is 25% to 50% and takes the form of conjunctivitis, iritis, and, rarely, a bilateral retinitis [3]. Other signs include cataract, glaucoma, aqueous cells, iris atrophy, and posterior synechiae. The retina of patients with congenital rubella is characterized by the classic saltand-pepper fundus along with normal-appearing blood vessels and an occasional pale optic nerve. Despite these retinal changes, vision is usually not affected. Glaucoma and keratitis may also be seen in patients with this condition and may affect vision. These ocular findings make up a part of the congenital rubella syndrome, which incorporates systemic findings such as heart defects, sensorineural hearing loss, mental and growth retardation, and hepatosplenomegaly. A summary of ocular findings associated with TORCHS syndromes may be found in Table 5.
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Table 5 Ocular findings associated with TORCHS syndromes Iritis Toxoplasmosis Rubella Cmv Herpes Syphilis a b c
Yes Yes No Yes Yes
Keratitis No Yes No Yes Yes
Cataract No Yes Yes No No
Glaucoma No Yes No Yesc Yes
Retinitis a
Yes Yesb Yesb Yes Yesb
Small eye No Yes Yes Yes Yes
macular or peripheral scars ‘‘salt and pepper’’ appearance when associated with iritis or iridocyclitis
Syphilis-associated uveitis Ocular involvement can be seen with either acquired or congenital forms of syphilis. In the congenital form, Treponema pallidum organisms can pass from placenta to the fetus. In addition to the eyes, syphilis can affect bone, bone marrow, central nervous system, liver, lungs, and spleen. Fundus examination may reveal a saltand-pepper or bone spicule chorioretinitis, along with pallor of the optic nerve. Iritis and interstitial keratitis may also be seen, the latter being incorporated into the so-called Hutchinson’s triad, which adds deafness and malformed incisors (known as Hutchinson’s teeth) [4]. In the acquired form, inflammation can be anterior or posterior. Posterior involvement can be in the form of vitritis, chorioretinitis, vasculitis, optic papillitis, or optic atrophy [4]. Syphilis-associated inflammation does not respond well to corticosteroids. Treatment varies with the stage of the disease; however, the criterion standard for treatment is 10 days of intravenous penicillin for congenital or neurosyphilis. Masquerade syndromes Conditions that mimic uveitis are known as masquerade syndromes. Although they may not be primarily infectious or inflammatory, their importance to the overall well being of the patient cannot be overlooked. These conditions must be considered in the differential diagnosis of ocular inflammation. Retinoblastoma Retinoblastoma is the most common malignant pediatric ocular tumor. It must be ruled out in any case of intraocular inflammation in a patient less than 5 years old. In retinoblastoma, both anterior and posterior segment inflammation may also be present. Occasionally, the retinoblastoma patient may present with a red, painful eye. On gross examination, one may even be able to see a pseudohypopyon which represents a layering of tumor cells in the anterior chamber. With exophytic tumors an endophthalmitic picture may be seen. These patients should be urgently referred to an ophthalmologist for a complete work up.
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Leukemia Ocular inflammation is seen in patients with acute lymphoblastic, acute myelogenous, and acute monocytic leukemia. The anterior segment findings include heterochromia, iris infiltrates, spontaneous hyphema, leukemic cells in the aqueous, or pseudohypopyon. Retinal involvement usually appears as dilated retinal vessels and retinal hemorrhages, some of which have white centers consisting of leukemic cells. Choroidal involvement, rarely detected clinically, is represented by leukemic infiltration. Optic nerve and orbital involvement are also seen fairly commonly. Juvenile xanthogranuloma Juvenile xanthogranuloma is a non-neoplastic histiocytic proliferation that usually develops in children under the age of 2 years. Children with juvenile xanthogranuloma can present with anterior chamber cell or spontaneous hyphema. There also may be iris heterochromia from the presence of fleshy, yellow-brown iris masses that can be localized or diffusely infiltrative. Skin examination may reveal one or more round, orange/tan papules. This condition is generally self-limited and will usually regress by age 5 years.
Summary Uveitis in children is an entity most pediatricians and ophthalmologists seldom encounter. It is prevalent in society, however, and the high incidence of sight-threatening complications in untreated children warrants a baseline knowledge of the diseases and disorders involved as well as a sense of when to refer to a specialist.
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