Uveitis, Anterior, Childhood Clinical Presentation

The main objective in taking the history in children with anterior uveitis is to narrow the differential diagnosis, to optimize laboratory testing, and to direct appropriate referrals.

The parents and the child, if appropriate, should be asked about the presence of arthritis, rashes or other dermatologic disorders, gastrointestinal disease, and asthma or other pulmonary conditions. The history is covered in more detail in the sections covering the specific causes of uveitis.

As in adult patients with uveitis, a complete examination of the eye and ocular adnexa is essential. Rarely, in younger patients or uncooperative patients, examination under anesthesia may be required.

• Inspect and palpate the lacrimal gland because it may be enlarged in sarcoidosis and other infiltrative conditions. Similarly, palpate the lymph nodes of the head and neck.
• When appropriate, inspect the skin of the entire body. Erythema nodosum is common in sarcoidosis but usually does not occur on the face. However, crops of papular eruptions may occur in a periocular distribution as a manifestation of sarcoidosis.
• Blepharitis and blepharoconjunctivitis may be signs of herpes simplex virus (HSV) infection. Careful inspection of the conjunctiva for granulomata is obviously a key part of the evaluation of any patient with uveitis.
• Yellow-orange periocular lesions may be a clue that intraocular inflammation is due to juvenile xanthogranuloma (JXG), as well as providing an easily accessible biopsy site.
• Corneal band keratopathy is often seen in JIA-associated uveitis; it may be quite subtle and limited to the limbal areas of the 3-o'clock and 9-o'clock meridians.
• Specifically seek evidence of geographic or stellate keratitis suggesting herpes infection; fluorescein or rose bengal staining helps to identify these signs.
• Mutton-fat keratic precipitates (KP) may be present in granulomatous conditions, but smaller KP occur in JIA-associated and HLA-B27–associated uveitis. Assess anterior chamber cell and flare according to a standard grading scheme.
• Examine the iris for Koeppe and Busacca nodules, which occur in granulomatous uveitis. Anterior and posterior synechiae suggest prior episodes or a prolonged course and indicate an increased likelihood of glaucoma.
• Pseudohypopyon may indicate leukemia, retinoblastoma, and JXG.
• Examine the vitreous for spillover inflammation, and exclude intermediate uveitis and pars planitis.
• Optic disc edema is uncommon but can occur. The edema typically resolves but often lags behind improvement of the uveitis.^[8]
• Determination of the intraocular pressure is critical but usually does not help to narrow the differential diagnosis.
• Arthritis and joint tenderness suggest JIA or spondyloarthropathy; limited torso flexion occurs in AS; and the development of a new heart murmur along with fever and rash may suggest Kawasaki disease.

• Juvenile idiopathic arthritis

  • JIA refers to arthritis of unknown cause in a child. The International League of Associations for Rheumatology (ILAR) classification of JIA includes 7 forms of the disease. Categories include systemic, oligoarticular, RF-negative polyarthritis, RF-positive polyarthritis, psoriatic, enthesitis-related, and undefined JIA. In the United States, JIA affects 60,000-70,000 children.
  • Uveitis can develop in children with oligoarthritis, RF-negative polyarthritis, enthesitis-related arthritis, and psoriatic JIA and can lead to long-term complications. A quiet, usually bilateral predominantly anterior uveitis is notorious for causing no symptoms in its early stages. As the inflammation continues, posterior synechiae, cataracts, glaucoma, and band keratopathy occur.
  • Males with JIA have a poorer visual prognosis. Children who develop uveitis prior to the onset of arthritis also have worse visual acuity during the first 3 years following the diagnosis of uveitis.^{[1, 9]}
• Reactive arthritis

  • The classic description of reactive arthritis is that of a triad of urethritis, conjunctivitis, and arthritis.
  • Acute or chronic nongranulomatous anterior uveitis occurs in reactive arthritis in as many as 30% of cases. Recurrent acute attacks are typical; both eyes are affected but usually not simultaneously. Posterior synechiae, fibrinous exudates, hypopyon formation, and hypotony are common. Spillover vitritis and cystoid macular edema may be seen.
  • The attacks typically last from 2-3 months. In children, disease onset may occur following enteritis due to Salmonella, Shigella, Yersinia, or Campylobacter species. Antecedent chlamydial urethritis has a greater role in adult cases.
  • Approximately 60% of patients have the HLA-B27 haplotype, and males are affected at least 5 times more frequently than females. Within weeks following an inciting infection, a peripheral arthritis develops, typically asymmetrically involving the hands, feet, knees, ankles, and wrists. Other characteristic lesions include superficial oral ulcers, keratoderma blennorrhagica, and balanitis circinata.
• Ankylosing spondylitis

  • AS is characterized by painful stiffening of the back caused by sacroiliitis and lumbosacral spondylitis. Lower back pain is the usual presenting symptom, although some patients have peripheral arthritis.
  • Of patients with AS, 90% have the HLA-B27 haplotype; however, unlike reactive arthritis, no other specific inciting cause is known.
  • Mean age of onset is 11.5 years, and males are 3 times more commonly affected than females. The uveitis is similar to that seen in reactive arthritis, as follows: recurrent, nongranulomatous anterior uveitis, frequently with fibrinous exudate, hypopyon formation, and posterior synechiae.
• Ulcerative colitis and Crohn disease

  • Compared to the previously discussed spondyloarthropathies, uveitis occurs less commonly in patients with inflammatory bowel disease. Overall, about 5% of patients develop iritis, which typically is mild anterior nongranulomatous. Patients often are asymptomatic.
  • Episcleritis also may occur in patients with inflammatory bowel disease. Whether the presence of uveitis parallels disease flare-ups is debated. Severe ocular sequelae are uncommon.
• Childhood sarcoidosis

  • Sarcoidosis is a chronic multisystem disorder with variable clinical manifestations that is uncommon in children.
  • In children younger than 5 years, the clinical manifestations differ from older children with sarcoidosis. In these children, the most common clinical findings include a maculopapular, erythematous rash; uveitis; and polyarticular arthritis. Additionally, pulmonary involvement is uncommon in this group of children.
  • In children 5 years and older, the most common clinical findings include lymphadenopathy, pulmonary abnormalities, and uveitis. The clinical course in these children is similar to that seen in adults with sarcoidosis.
  • Ocular involvement is common in children with sarcoidosis. Anterior uveitis is the most common ocular manifestation in these children. The uveitis may be characterized as granulomatous or nongranulomatous. Ocular findings include KP, iris nodules, cells and flare, and posterior synechiae. Band keratopathy frequently is seen in children with chronic inflammation. Posterior uveitis and disc edema also can occur. Secondary glaucoma is not uncommon and can result in permanent visual loss.
  • Children who have findings suggestive of sarcoidosis should undergo a complete examination by a pediatrician. The examination should include a thorough evaluation of the lungs and a determination of serum and urine calcium levels. Additionally, these children should undergo complete examination by an ophthalmologist.
• Kawasaki disease

  • Kawasaki disease is a systemic disease of unknown cause affecting children and adolescents. Its major features are protracted fever, cervical lymph node swelling, strawberry tongue (prominence of tongue papillae), palmar erythema, erythematous rash, and bilateral conjunctival injection.
  • Occurrence of uveitis was not recognized in the early descriptions of Kawasaki disease but a self-limited, nongranulomatous anterior uveitis is very common, particularly in the early stages of the disease.
• Viral-associated diseases (eg, mumps, measles, varicella, mononucleosis): Mild, bilateral nongranulomatous, anterior uveitis is common in systemic viral illnesses such as those noted above. Patients typically are asymptomatic, and the uveitis is self-limited.
• Rubella virus: Chronic anterior uveitis with stellate keratic precipitates may occur in unvaccinated children. Cataract is not uncommon in these children.^[10]
• Juvenile xanthogranuloma: Intraocular JXG, usually presenting as an iris mass, may produce a picture resembling anterior uveitis. Characteristic yellow-cream lesions of the skin may be present, providing a convenient site to biopsy. Spontaneous hyphema also may occur.
• Leukemia: Anterior uveitis may rarely signal the onset of or a relapse of leukemia. A hypopyon may be present.
• Acute tubulointerstitial nephritis and uveitis

  • Acute tubulointerstitial nephritis and uveitis (TINU syndrome) consists of acute interstitial nephritis and uveitis. Most patients are adolescents with a median age of 15 years, although middle-aged and elderly patients have been reported. Most patients exhibit proteinuria, elevated urine beta-2-microglobulin, glucosuria, and sterile pyuria. Serum creatinine is also elevated. Additional findings include fever, weight loss, fatigue, anorexia, anemia, and hypergammaglobulinemia.
  • The most common ocular manifestation of TINU syndrome is an acute bilateral anterior uveitis. The uveitis typically responds to treatment with corticosteroids but may become recurrent. Less common manifestations include vitritis, panuveitis, retinal vasculitis with perivascular sheathing, and rarely multifocal choroiditis.
  • To establish a diagnosis of TINU, the onset of uveitis should occur within a year of the development of acute interstitial nephritis.^[11]
• Poststreptococcal syndrome uveitis: Rarely, bilateral nongranulomatous anterior uveitis can develop 1-8 weeks following group A streptococcal infection.^[12] Posterior segment involvement has been reported but is much less common. Antistreptococcal lysin O titers are elevated. Management with pediatric subspecialists is essential (see Consultations).
• Blau syndrome

  • Familial granulomatous arthritis, iritis, and rash (Blau syndrome) is an autosomal dominant multisystem inflammatory disease first described in 1985.
  • Clinical manifestations of Blau syndrome include arthritis, synovial cysts, camptodactyly, erythematous rash, and uveitis. Clinical findings are similar to those seen in childhood sarcoidosis; however, synovial cysts and camptodactyly have not been described in children with sarcoidosis. Additionally, pulmonary involvement has not been described in children or adults with Blau syndrome.
  • The rash seen in Blau syndrome is a granulomatous erythematous papular eruption described as painless, tiny, red dots often in a generalized distribution. Onset usually is in early childhood, but it can occur as early as age 4 months. In most cases, the rash resolves spontaneously.
  • Joint manifestations typically develop during childhood and often before age 10 years. The earliest joint changes are insidious in onset and include synovial cysts and boutonniere deformities. Painless synovial cysts may develop on the wrists, ankles, or dorsum of the foot. Boutonniere deformities of the fingers are a characteristic finding in these children. These early lesions often progress to camptodactyly and cystic swelling of the wrists, elbows, knees, and ankles.
  • Ocular involvement appears to be the most serious complication of Blau syndrome. Uveitis can develop in childhood or during the early adult years. In most cases, the uveitis initially manifests as a nongranulomatous anterior uveitis; however, the disease often is recurrent and eventually develops into a chronic anterior uveitis. Later in the clinical course, posterior uveitis can occur with vitritis, disc edema, and chorioretinal lesions. Secondary glaucoma is not uncommon and may lead to devastating visual loss.
• Herpes simplex

  • Uveitis associated with herpes simplex often is accompanied by keratitis, making diagnosis relatively straightforward. Whether the inflammation represents active infection or an immune reaction is an unsettled question.
  • The inflammation may be severe, with pain, KP, and hypopyon formation. Trabeculitis with secondary glaucoma is an important complication.
• Varicella zoster

  • Varicella zoster in children usually occurs in the setting of immunosuppression, such as in acquired immunodeficiency syndrome (AIDS).
  • Keratitis usually is seen with the uveitis that may occur. The uveitis is believed to result from vasculitis, with resultant vascular occlusion and ischemia.
• Behçet disease

  • Behçet disease is a systemic vasculitis characterized by recurrent oral aphthous ulcers, genital ulcers, and uveitis. Additional manifestations are variable but may include skin lesions, venous thrombosis, arthritis, and central nervous system symptoms. Most affected patients are aged 25-35 years. However, children can be affected.
  • Children with Behçet disease may develop anterior uveitis, posterior uveitis, or panuveitis. A retrospective report from Turkey found that among children, 33% had anterior uveitis.^[13]