Pediatrics
Uveitis
- OVERVIEW: What every practitioner needs to know
- Are you sure your patient has uveitis?
-
What other disease/condition shares some of these symptoms?
-
What caused this disease to develop at this time?
-
What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?
-
Would imaging studies be helpful? If so, which ones?
- If you are able to confirm that the patient has uveitis, what treatment should be initiated?
-
What are the adverse effects associated with each treatment option?
-
What are the possible outcomes of uveitis?
-
What causes this disease and how frequent is it?
-
How do these pathogens/genes/exposures cause the disease?
-
Other clinical manifestations that might help with diagnosis and management
-
What complications might you expect from the disease or treatment of the disease?
-
Are additional laboratory studies available; even some that are not widely available?
-
How can uveitis be prevented?
-
What is the evidence?
-
Ongoing controversies regarding etiology, diagnosis, treatment
OVERVIEW: What every practitioner needs to know
Are you sure your patient has uveitis?
Uveitis is a group of disorders characterized by the presence of intraocular inflammation. There are many causes of uveitis with numerous clinical manifestations. Referral to an ophthalmologist is always necessary to confirm the presence of intraocular inflammation. If uveitis is suspected, the patient should be evaluated by an ophthalmologist within 72 hours.
The diagnosis and management of uveitis in children can be difficult. Compared with adults, history-taking and examination can be challenging, delayed diagnosis occurs frequently, there is potential for long-term disability, and young children can develop amblyopia. For these reasons, it is important to refer these patients to ophthalmologists who are familiar with the evaluation and management of children with uveitis.
Anatomic Location
The location of the inflammation within the eye will often determine the clinical manifestations in a given patient. In addition, the location helps establish a focused differential diagnosis, aids in the choice of therapy, and may predict overall prognosis. A complete ophthalmic evaluation with dilated fundus examination is required to determine the location of the inflammation. The terminology used to describe the location of the inflammation is listed below:
Anterior uveitis : inflammation confined to the anterior chamber. Mild inflammation may be present in the anterior vitreous. Older terms include iritis and iridocyclitis.Intermediate uveitis : inflammation primarily of the vitreous and peripheral retina. Spillover anterior uveitis is not uncommon but typically mild. Previously used terms include vitritis, pars planitis, and cyclitis.Posterior uveitis : inflammation primarily of the retina, choroid, or both. Terms include retinitis, choroiditis, retinochoroiditis, and chorioretinitis.Panuveitis : inflammation involving all three compartments--anterior chamber, vitreous, and retina and/or choroid.
Symptoms and Signs
Symptoms and signs of uveitis differ based upon several factors. The location and severity of the inflammation are major determinants of clinical manifestations in most patients. Clinical manifestations may also be different in patients with acute onset compared to those with chronic uveitis. Juvenile idiopathic arthritis (JIA) associated uveitis is an exception since it often has few if any symptoms and signs even when there is active inflammation.
Anterior uveitis
Pain, decreased vision possible, photophobia
Redness
Intermediate uveitis
Floaters, decreased vision
Photophobia and pain (less common)
Posterior uveitis
Decreased vision, floaters
Scotomata
Panuveitis
Any or all of the above symptoms for other forms of uveitis
Etiology
Uveitis is often categorized into one of several groups based upon the etiology of the disease. Three broad categories include noninfectious uveitis, infectious uveitis, and masquerade syndromes.
Noninfectious uveitis
Idiopathic
Juvenile idiopathic uveitis (JIA)
HLA-B27 associated uveitis
Reiter's syndrome
Inflammatory bowel disease
Ankylosing spondylitis
Sarcoidosis
Traumatic iritis
Tubulointerstitial nephritis and uveitis (TINU) syndrome
Vogt-Koyanagi-Harada (VKH) disease
Sympathetic ophthalmia
Kawasaki disease
Multiple sclerosis
Behçet's disease
Blau syndrome
Chronic infantile neurological cutaneous and articular/neonatal onset multisystem inflammatory syndrome (CINCA/NOMID)
Infectious uveitis
Toxoplasmosis
Toxocariasis
Diffuse unilateral subacute neuroretinitis (DUSN)
Herpes simplex
Varicella zoster
Cytomegalovirus
West Nile virus
Post-viral (measles, mumps, mononucleosis)
Rubella
Post-streptococcal syndrome
Cat-scratch disease
Lyme disease
Syphilis
Tuberculosis
Endogenous endophthalmitis
Masquerade syndromes
Leukemia
Lymphoma
Retinoblastoma
Juvenile xanthogranuloma (JXG)
Occult intraocular foreign body
Coat's disease
Retinitis pigmentosa
What other disease/condition shares some of these symptoms?
Infectious conjunctivitis
Allergic conjunctivitis
Corneal abrasion
Corneal foreign body
Conjunctival foreign body
Blepharoconjunctivitis
Keratitis
Cellulitis
What caused this disease to develop at this time?
Infectious forms of uveitis result from infection with the specific organism. In patients with some forms of infectious uveitis, such as toxoplasmosis, herpes simplex, and varicella zoster, recurrent episodes can occur despite prior treatment with antimicrobials.
Noninfectious forms of uveitis may develop as an isolated ocular disease or be associated with an underlying systemic disease.
Mechanisms for initiation of inflammation in these forms of uveitis likely involve one or more factors including:
Microbial infection resulting in molecular mimicry or activation of innate immunity
Trauma
Genetic factors
What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?
The treating ophthalmologist may obtain laboratory tests based upon the likely diagnosis and their experience with uveitis in children. In some cases, the ophthalmologist may request that the pediatric specialist assist in the work-up of the child with uveitis. As such, it is important for pediatric specialist to have a working knowledge of the spectrum of diseases associated with uveitis in children.
If the pediatric specialist is consulted to evaluate for an underlying etiology, it is important for the ophthalmologist to indicate the anatomic location of the uveitis and/or the possible etiologies. This communication will greatly improve the evaluation provided since the pediatric specialist will focus his/her efforts on a limited group of likely disorders.
Table I.
Laboratory studies for the evaluation of children with uveitis
Type of Uveitis | Laboratory Tests |
---|---|
Anterior uveitis | CBC with differential, ANA, HLA-B27, FTA-ABS, ESR, urinalysis, urine beta-2 microglobulin, antistreptococcal lysin O serology, TB testing |
Intermediate uveitis | CBC with differential, FTA-ABS, serum angiotensin converting enzyme, ESR, urinalysis, urine beta-2 microglobulin, toxoplasma serology, toxocara serology, TB testing, cerebrospinal fluid analysis (if suspicious for multiple sclerosis) |
Posterior uveitis | CBC with differential, serum angiotensin converting enzyme, toxoplasma serology, toxocara serology, FTA-ABS, B. henselae serology, B.burgdorferi serology, West nile virus serology |
Suspected masquerade (leukemia or lymphoma) | CBC with differential, additional testing as indicated |
Would imaging studies be helpful? If so, which ones?
Imaging studies have limited utility in the evaluation of children with uveitis. If the following diseases are suspected, imaging may be useful.
Sarcoidosis: chest x-ray. if not diagnostic and high index of suspicion exists, consider high resolution CT of chest
Toxoplasmosis: if child is immunosuppressed with evidence of ocular toxoplasmosis, consider MRI of the brain
Retinoblastoma: ultrasound of the eye, CT and MRI of the head and orbits
Pediatric onset multiple sclerosis: MRI of the brain
Occult intraocular foreign body: CT of the orbits with 0.5 mm cuts (helical scan may be best technique if available)
If you are able to confirm that the patient has uveitis, what treatment should be initiated?
Treatment of children with uveitis typically depends upon the etiology of the inflammation. Treatment recommendations are similar for many noninfectious forms of uveitis, while infectious uveitis requires specific therapy based upon the microbial pathogen.
Treatment of Noninfectious Uveitis
Most children with noninfectious forms of anterior uveitis are managed primarily by the ophthalmologist. The one exception is children with juvenile idiopathic uveitis (JIA). All of these patients are best managed using a team approach with an ophthalmologist and pediatrician or pediatric rheumatologist.
Children with the following forms of uveitis will likely require management using a team approach with an ophthalmologist and pediatrician or pediatric rheumatologist since most will require systemic therapy:
Intermediate uveitis not controlled with periocular corticosteroids
Noninfectious posterior uveitis
Noninfectious panuveitis
Several systemic medications have been used for children with uveitis. If systemic corticosteroids are utilized, the duration of treatment should be minimized to avoid significant side effects. The choice of specific medication often depends upon the underlying disease, comorbid conditions, anticipated compliance, and side effect profile. Systemic agents used in children include:ss
Prednisone--short-term only
Methotrexate
Azathioprine
Mycophenolate mofetil
Cyclosporine
Infliximab
Adalimumab
A general outline for treating children with noninfectious uveitis is shown in
Table II .
Table II.
Therapy for children with noninfectious uveitis
Type of Uveitis | Topical Therapy | Periocular Therapy | Systemic Therapy |
---|---|---|---|
Anterior | Typically initial treatment; corticosteroids, cycloplegics | For severe cases not controlled with topical therapy | For severe chronic anterior uveitis not controlled with topical and/or periocular therapy. All children with JIA should receive systemic therapy. |
Intermediate | Corticosteroids, cycloplegics if anterior inflammation present | Often used as initial therapy | For cases not controlled with periocular therapy, or those with persistent inflammation despite laser or cryotherapy |
Posterior | Corticosteroids, cycloplegics if anterior inflammation present | May be useful for noninfectious forms of uveitis | Many/most will require systemic therapy to control the inflammation |
Panuveitis | Corticosteroids, cycloplegics if anterior inflammation present | May be useful for noninfectious forms of uveitis | Many/most will require systemic therapy to control the inflammation |
Masquerade | Treatment of the underlying disease once diagnosis established. |
Treatment of Infectious Uveitis
Treatment of children with infectious forms of uveitis typically requires systemic antimicrobial therapy. Most cases of infectious uveitis are treated in an outpatient setting. The treating ophthalmologist will usually consult the pediatric specialist to aid in the treatment of some forms of infectious uveitis such as those with systemic manifestations (e.g. syphilis, tuberculosis, Lyme disease, etc.).
Anti-inflammatory therapy is often required in addition to antimicrobial therapy in many patients. Depending upon the specific pathogen, local therapy may include the following:
Topical corticosteroids
Topical cycloplegics
Periocular corticosteroids (should never be used for toxoplasmosis)
Oral corticosteroids
Treatment recommendations for specific infections are outlined in
Table III.
Treatment for children with infectious uveitis
Infection | Treatment | Other Treatment Options |
---|---|---|
Toxoplasmosis | Classic "triple therapy" includes pyrimethamine, sulfadiazine, and prednisone for 6 weeks | Several emerging treatment options are used increasingly:Trimethoprim (80 mg)/sulfamethoxazole (400mg) twice daily for 6 weeksAzithromycin with pyrimethamine daily for 4 weeksAzithryomycin daily for 5 weeksAtovaquone qid for 1-3 monthsIntravitreal clindamycin with dexamethasone |
Toxocariasis | Systemic and/or periocular corticosteroids | Pars plana vitrectomy in some cases |
Diffuse unilateral subacute neuroretinitis (DUSN) | Laser photocoagulation of nematode | If nematode cannot be located, treatment with oral albendazole 200 mg for one month may result in immobilization of the nematode |
Herpes simplex (anterior uveitis) | Topical corticosteroids | Long-term (12-18 months) low dose antiviral agents may be useful in preventing recurrences. Oral acyclovir 400 mg bid, orOral valacyclovir 500 mg daily |
Varicella zoster (anterior uveitis) | Topical corticosteroids | Oral acyclovir 5 times daily for 10 days orFamciclovir daily for 10 days (but no controlled studies for this drug in uveitis) |
Acute retinal necrosis (herpes simplex or varicella zoster) | Intravenous acyclovir 10 mg/kg daily (3 divided doses) until cessation of active retinitis (typically 10-21 days) followed by oral acyclovir for 3 months | Patients who do not respond to intravenous acyclovir may benefit from intravitreal ganciclovir plus foscarnet with oral valacyclovirOral famciclovir or valacylovir has been used in a limited number of patients, but guidelines for using oral therapy only have not been established |
Cytomegalovirus | Treatment decisions typically based upon immune status of child. If treatment is necessary, specific drug and dosage determined by pediatric specialist. | |
West Nile virus | Topical corticosteroids for anterior uveitis | No clear indications for treatment of posterior uveitis |
Post-viral | Most require no therapy. If child is symptomatic, may require topical corticosteroids. | |
Rubella | None for congenital infection. May benefit from topical corticosteroids in acquired disease. | |
Post-streptococcal syndrome | Topical and/or systemic corticosteroids | Systemic penicillins have been used, but no consensus regarding indications for use |
Cat-scratch disease | Topical corticosteroids for anterior uveitis | No clear guidelines regarding use of antibiotics for vitritis, chorioretinitis, or neuroretinitis. If severe, consult pediatric infectious disease specialist. |
Lyme disease | Topical corticosteroids for anterior uveitis | The presence of uveitis should prompt a systemic evaluation by a pediatric specialist and include lumbar puncture. Specific antibiotic treatment is based upon results of this evaluation. |
Syphilis | Topical corticosteroids for anterior uveitis | Patients with syphilitic uveitis require a systemic evaluation by a pediatric specialist to determine the stage of the disease and appropriate antibiotic therapy. |
Tuberculosis | Topical corticosteroids for anterior uveitis | Systemic therapy is required for all patients with uveitis associated with tuberculosis. Evaluation and selection of appropriate antibiotic therapy is determined by the pediatric specialist. |
Endogenous endophthalmitis | Systemic antifungal or antibiotic therapy based upon the specific organism | Most patients have an underlying infection and are already receiving antimicrobial therapy. In severe cases, intravitreal antifungal agents may be useful. |
What are the adverse effects associated with each treatment option?
Topical corticosteroids
Increased intraocular pressure
Glaucoma
Cataract formation
Periocular corticosteroids
Increased intraocular pressure
Glaucoma
Cataract formation
Ptosis
Hypopigmentation of eyelid skin at site of injection
Topical cycloplegics
Tachycardia
Skin flushing
Dry mouth
Fever
Irritability
Drowsiness
Mental status changes
Delirium
Blurred vision
Prednisone
Growth suppression
Cushingoid habitus
Hyperglycemia
Diabetes mellitus
Hypertension
Adrenocortical insufficiency
Myopathy
Delayed wound healing
Avascular necrosis of bone
Osteoporosis
Irritability
Depression
Euphoria
Increased risk for infections
Increased intraocular pressure
Glaucoma
Cataract formation
Methotrexate
Nausea/vomiting
Diarrhea
Hepatoxicity
Pneumonitis
Pulmonary fibrosis
AzathioprineAzathioprine
Leukopenia
Thrombocytopenia
Nausea/vomiting
Diarrhea
Hepatotoxicity
Pancreatitis
Interstitial pneumonitis
Secondary infections
Mycophenolate mofetil
Neutropenia
Pure red cell aplasia (PRCA)
Nephrotoxicity
Hepatotoxicity
Nausea
Increased risk for infections
Progressive multifocal leukoencephalopathy (PML)
Increased risk for lymphoproliferative disease or lymphoma
CyclosporineCyclosporine
Nephrotoxicity
Hypertension
Anemia
Nausea
Diarrhea
Gingival hyperplasia
Hirsutism
Paresthesias
Increased risk for opportunistic infections
Infliximab Infliximab
Infusion reactions
Headache
Nausea
Diarrhea
Abdominal pain
Upper respiratory infections
Increased ALT
Development of antinuclear antibodies
Development of antibodies to double-stranded DNA
Adalimumab
Injection site reactions
Headache
Rash
Antibodies to adalimumab
Development of antinuclear antibodies
Upper respiratory tract infections
Nausea
Abdominal pain
What are the possible outcomes of uveitis?
The prognosis for children likely differs by anatomic location of the uveitis, etiology, duration, treatment, chronicity, complications, and length of time between diagnosis and referral to a uveitis specialist. Complications occur in up to 76% of children. Up to 36% of children will develop moderate visual loss (visual acuity 20/50 or worse). Approximately 19% of children with uveitis will become legally blind in one eye.
Risk factors for poor visual outcome:
Posterior uveitis
Infectious uveitis; especially toxoplasmosis
Risks and benefits of the available treatment options
Topical corticosteroids: Highly beneficial; minimal risk in most cases.
Topical cycloplegics: Beneficial; minimal risk in most cases
Oral prednisone: Highly beneficial in severe cases; significant risk to children, especially if used for more than 3 months
Immunosuppressive therapy: Highly beneficial in severe or recalcitrant uveitis; significant risk that varies with specific drug
Biologic therapy: Long-term outcomes have not been described. Short-term outcomes indicate these agents may be highly beneficial in children who fail or have little response with traditional immunosuppressive therapy. Risk is probably less than other immunosuppressive agents. At present, cost is a major limiting factor.
What causes this disease and how frequent is it?
Estimates of the incidence of uveitis in children in North America and Europe are 4.3-6/100,000 population. The prevalence of childhood uveitis is approximately 30/100,000 population. All ages of children are affected. In a multicenter study, approximately 2/3 of cases were diagnosed between 6 and 15 years of age. Predisposing exposures include a limited number of microbial pathogens.
How do these pathogens/genes/exposures cause the disease?
N/A
Other clinical manifestations that might help with diagnosis and management
Risk factors for endogenous endophthalmitis include the following:
Premature infant
Immunosuppressed children
Sepsis
Diabetes mellitus
Hyperalimentation
Indwelling catheters
Post-organ transplantation
Recent abdominal surgery
Intravenous drug use
What complications might you expect from the disease or treatment of the disease?
Children less than 8 years of age are at risk for amblyopia if vision is impaired by the disease or its complications.
The complications of uveitis vary by anatomic location and etiology of the disease. Common complications are outlined in
Table IV.
Common complications of uveitis
Type of Uveitis | Common Complications |
---|---|
Anterior uveitis | Posterior synechiae, cataract, increased intraocular pressure, glaucoma, band keratopathy, cystoid macular edema |
Intermediate uveitis | Cataract, band keratopathy, increased intraocular pressure, glaucoma, cystoid macular edema, vitreous hemorrhage, retinal detachment |
Posterior uveitis | Cataract, increased intraocular pressure, glaucoma, cystoid macular edema, retinal or chorioretinal scars, choroidal neovascularization, permanent scotomata, retinal detachment. |
Panuveitis | Posterior synechiae, cataract, increased intraocular pressure, glaucoma, band keratopathy, cystoid macular edema, retinal or chorioretinal scars, choroidal neovascularization, permanent scotomata, retinal detachment. |
Are additional laboratory studies available; even some that are not widely available?
In cases suspicious for an infectious etiology and negative laboratory testing, polymerase chain reaction (PCR) of intraocular fluids may identify the organism. In most of these cases, vitreous biopsy or, less commonly, aqueous humor paracentesis is performed to obtain specimens for analysis. Currently there are a limited number of laboratories certified to perform PCR analysis of intraocular fluids.
How can uveitis be prevented?
In most cases, uveitis cannot be prevented. For some forms of infectious uveitis, avoiding possible exposures may be helpful (e.g., precautions to avoid tick bites if located in endemic regions for Lyme disease).
What is the evidence?
Smith, JA, Mackensen, F, Sen, HN. "Epidemiology and course of disease in childhood uveitis". Ophthalmology. vol. 116. 2009. pp. 1544-51.
(Large retrospective study from four centers in the United States.)Kump, LI, Cervantes-Castañda, RA, Androudi, SN. "Analysis of pediatric uveitis cases at a tertiary referral center". Ophthalmology. vol. 112. 2005. pp. 1287-92.
(Large retrospective study from a single U.S. tertiary referral center.)de Boer, J, Wulffraat, N, Rothova, A. "Visual loss in uveitis of childhood". Br J Ophthalmol. vol. 87. 2003. pp. 879-84.
(Large retrospective study from a single university hospital in the Netherlands.)Cunningham, ET. "Uveitis in children". Ocul Immunol Inflamm. vol. 8. 2000. pp. 251-61.
(Review article describing the prevalence of uveitis in children.)Holland, GN, Stiehm, ER. "Special considerations in the evaluation and management of uveitis in children". Am J Ophthalmol. vol. 135. 2003. pp. 867-78.
(Literature review and discussion from an international workshop regarding diagnosis and management of children with uveitis.)Habot-Wilner, Z, Sallam, A, Roufas, A. "Periocular corticosteroid injection in the management of uveitis in children". Acta Ophthalmol. vol. 88. 2010. pp. e299-304.
(Retrospective series of 15 children demonstrating efficacy of periocular corticosteroids in controlling uveitis.)Zierhut, M, Doycheva, D, Biester, S. "Therapy of uveitis in children". Int Ophthalmol Clin. vol. 48. 2008. pp. 131-52.
(Review article of therapeutic options with several algorithms used by the authors.)Saurenmann, RK, Levin, AV, Rose, JB. "Tumour necrosis factor alpha inhibitors in the treatment of childhood uveitis". Rheumatology (Oxford). vol. 45. 2006. pp. 982-9.
(Small retrospective series of children treated with TNF alpha inhibitors after failing standard immunosuppressive therapy.)Ardoin, SP, Kredich, D, Rabinovich, E. "Infliximab to treat chronic noninfectious uveitis in children: retrospective case series with long-term follow-up". Am J Ophthalmol. vol. 144. 2007. pp. 844-9.
(Small retrospective series of children treated with infliximab.)Schatz, CS, Uzel, JL, Leininger, L. "Immunosuppressants used in a steroid-sparing strategy for childhood uveitis". J Pediatr Ophthalmol Strabismus. vol. 44. 2007. pp. 28-34.
(Retrospective series of 40 children treated with systemic corticosteroids combined with either azathioprine or mycophenolate mofetil.)Sobrin, L, Kim, EC, Christen, W. "Infliximab therapy for the treatment of refractory ocular inflammatory disease". Arch Ophthalmol. vol. 125. 2007. pp. 895-900.
(Retrospective series of 27 children treated with infliximab following failure of conventional immunosuppressive therapy.)Rosenberg, KD, Feuer, WJ, Davis, JL. "Ocular complications of pediatric uveitis". Ophthalmology. vol. 111. 2004. pp. 2299-306.
(Retrospective series of 148 children describing ocular complications of uveitis)Soheilian, M, Rmezani, A, Azimzadeh, A. "Randomized trial of intravitreal clindamycin and dexamethasone versus pyrimethamine, sulfadiazine, and prednisolone in the treatment of ocular toxoplasmosis". Ophthalmology. vol. 118. 2011. pp. 134-41.
(Prospective, randomized trial of adults with active toxoplasmosis; no significant difference between intravitreal therapy and classic therapy)Bosch-Driessen, LH, Verbraak, FD, Suttorp-Schulten, MS. "A prospective, randomized trial of pyrimethamine and azithromycin vs pyrimethamine and sulfadiazine for the treatment of ocular toxoplasmosis". Am J Ophthalmol. vol. 134. 2002. pp. 34-40.
(Prospective multicenter randomized open-label trial showing equivalent efficacy in treating ocular toxoplasmosis)Rothova, A, Bosch-Driessen, LH, vanLoon, NH, Treffers, W. "Azithromycin for ocular toxoplasmosis". Br J Ophthalmol. vol. 82. 1998. pp. 1306-8.
(Small interventional case series describing effectiveness of azithromycin as single drug therapy.)Pearson, PA, Piracha, AR, Sen Ha, Jaffe, GJ. "Atovaquone for the treatment of toxoplasma retinochoroiditis in immunocompetent patients". Ophthalmology. vol. 106. 1999. pp. 148-53.
(Prospective, randomized open-label trial of 17 patients demonstrating favorable response to therapy with limited side effects.)Souza, EC, Casella, AM, Nakashima, Y, Monteiro, ML. "Clinical features and outcomes of patients with diffuse unilateral subacute neuroretinitis treated with oral albendazole". Am J Ophthalmol. vol. 140. 2005. pp. 437-45.
(Interventional case series of 12 children and adults demonstrating safety and benefit of albendazole.)"A controlled trial of oral acyclovir for the prevention of stromal keratitis or iritis in patients with herpes simplex virus epithelial keratitis. The epithelial keratitis trial. The Herpetic Eye Disease Study Group ". Arch Ophthalmol. vol. 115. 1997. pp. 703-12.
(Randomized, masked, placebo controlled trial of oral acyclovir in patients age 12 or older; results suggest acyclovir may be beneficial in reducing recurrences of uveitis.)Aizman, A, Johnson, MW, Elner, SG. "Treatment of acute retinal necrosis syndrome with oral antiviral medication". Ophthalmology. vol. 114. 2007. pp. 307-12.
(Small, nonrandomized interventional series of adults and one child treated with famciclovir or valacyclovir for acute retinal necrosis.)Wormser, GP, Dattwyler, RJ, Shapiro, ED. "The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: clinical practice guidelines by the infectious diseases society of America". Clin Infect Dis. vol. 43. 2006. pp. 1089-134.
(2006 guidelines for both children and adults with Lyme disease.)Aldave, AJ, King, JA, Cunningham, ET. "Ocular syphilis". Curr Opin Ophthalmol. vol. 12. 2001. pp. 433-41.
(Review article describing ocular manifestations of congenital and acquired syphilis)Woods, CR. "Syphilis in children: congenital and acquired". Semin Pediatr Infect Dis. vol. 6. 2005. pp. 245-57.
(Review of congenital and acquired syphilis in children.)Lerman, MS, Burnham, JM, Change, PY. "Response of pediatric uveitis to tumor necrosis factor-α inhibitors". J Rheumatol. vol. 40. 2011. pp. 1394-403.
(Retrospective review of children with uveitis treated with anti-TNF therapy at five uveitis centers.)Slabaugh, MA, Herligh, E, Ongchin, S, vanGelder, RN. "Efficacy and potential complications of difluprednate use for pediatric uveitis". Am J Ophthalmol. vol. 153. 2012. pp. 932-8.
(Case series of children treated with difluprednate with high rate of elevated intraocular pressure and cataract formation.)Lerman, MS, Burnham, JM, Change, PY. "Response of pediatric uveitis to tumor necrosis factor-α inhibitors". J Rheumatol. vol. 40. 2011. pp. 1394-403.
(Retrospective review of children with uveitis treated with anti-TNF therapy at five uveitis centers.)Slabaugh, MA, Herligh, E, Ongchin, S, vanGelder, RN. "Efficacy and potential complications of difluprednate use for pediatric uveitis". Am J Ophthalmol. vol. 153. 2012. pp. 932-8.
(Case series of children treated with difluprednate with high rate of elevated intraocular pressure and cataract formation.)Ongoing controversies regarding etiology, diagnosis, treatment
N/A
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