Part 2 • Diagnosis

Once the above questions are answered, lists of possible diagnoses are generated. By determining the diagnoses that appear most frequently, a final list of the most likely conditions responsible for the patient’s uveitis is generated. The clinician can then order diagnostic studies to discern among them. The following cases will help to illustrate the process of developing a differential diagnosis in the patient with uveitis.

Table 4-5  Common causes of anterior and posterior uveitis

*Data from Perkins ES, Folk J. Uveitis in London and Iowa. Ophthalmologica 1984; 36: 189.

†Data from Henderly DE, Genstler AJ, Smith RE, et al. Changing patterns of uveitis. Am J Ophthalmol 1987; 103: 131–6.

Case 4-1

A 42-year-old white woman presented with a 10-year history of bilateral uveitis treated intermittently with topical and systemic corticosteroids and a chief complaint of blurred vision that was worse in the left eye. A detailed medical history was significant for sinusitis and depression. On examination, her visual acuity was 20/50 in the right eye and 20/100 in the left. Slit-lamp biomicroscopy showed mutton-fat KPs in the left eye. There were trace vitreous cells and haze in the right eye and 2+ vitreous cells and haze in the left eye. There were peripheral retinal vasculitis and cystoid macular edema in both eyes (Fig. 4-1). Physical examination revealed no rash, joint findings, or other abnormalities. Neurologic examination was normal.

Most clinicians will find it difficult to derive an erudite differential diagnosis from simply reading this case history, but by classifying the uveitis with the eight questions previously outlined, lists of possible diagnoses can be generated. By comparing these lists, the most likely diagnoses can then be identified. Question 1 asks whether the disease is acute or

Figure 4-1.  Late phase of fluorescein angiogram showing staining of blood vessel walls and leakage of dye from peripheral retinal vasculature.

chronic. Because the patient has a 10-year history of disease, the uveitis is clearly chronic and this is associated with the diseases listed in Box 4-2. The patient has mutton-fat KPs, suggesting that the uveitis is granulomatous, and this suggests the list of diagnoses shown in Box 4-3. The disease is bilateral, which does not point to a specific set of diseases; however, with prominent vitritis and peripheral retinal vasculitis, the anatomic classification of an intermediate uveitis does suggest a specific set of possible diseases to the clinician (Box 4-6). The patient is white and in the 24–45-year age range, suggesting the diagnoses shown in Table 4-2. As seen in Table 4-4, a complaint of sinusitis suggests a possible diagnosis of Wegener’s granulomatosis, but the patient had no specific findings on physical examination.

In summary, the uveitis can be classified as a chronic, granulomatous, bilateral, intermediate uveitis in a middle-aged white woman with intermittent response to topical and systemic corticosteroids. The lists containing possible diagnoses for this patient are shown in Box 4-9. If you compare these lists, the most frequently mentioned disorders include sarcoidosis, other causes of intermediate uveitis such as multiple sclerosis and inflammatory bowel disease, and other chronic disorders such as Behçet’s disease and Wegener’s granulomatosis. Diagnostic tests were then ordered to discern between the most likely disorders. Results of a diagnostic evaluation for sarcoidosis and Wegener’s granulomatosis, including a chest X-ray, serum angiotensin-converting enzyme level, antineutrophil cytoplasmic antibody test, and CT scan of the sinuses, were normal. However, an MRI scan of the brain revealed lesions consistent with a diagnosis of multiple sclerosis. The patient later developed an episode of lower extremity weakness followed by a second episode of paresthesia that extended to the level of the umbilicus that was diagnostic of this disease.

Case 4-2

A 73-year-old white woman presented with blurred vision in both eyes that had been present during the previous year. The patient first noted floaters in the left eye 1 year ago, but did not see an ophthalmologist until 3 months earlier, when she was

Classifying uveitis

Box 4-9  Lists of diagnoses generated for Case 4-1

Chronic, granulomatous, bilateral, intermediate uveitis in a middle-aged white woman with intermittent response to topical and systemic corticosteroids

CHRONIC UVEITIS

Juvenile rheumatoid arthritis Birdshot choroidopathy Serpiginous choroidopathy Tuberculous uveitis

Postsurgical uveitis (Propionibacterium acnes, fungal) Intraocular lymphoma

Sympathetic ophthalmia Multifocal choroiditis Sarcoidosis

Intermediate uveitis/pars planitis INTERMEDIATE UVEITIS Sarcoidosis

Inflammatory bowel disease Multiple sclerosis

Lyme disease Pars planitis

GRANULOMATOUS INFLAMMATION IN EYE Sarcoidosis

Sympathetic ophthalmia

Uveitis associated with multiple sclerosis Lens-induced uveitis

Intraocular foreign body Vogt–Koyanagi–Harada syndrome Syphilis

Tuberculosis

Other infectious agents AGE 25–45 YR Ankylosing spondylitis Idiopathic anterior uveitis

Fuchs’ heterochromic iridocyclitis Intermediate uveitis Toxoplasmosis

Behçet’s disease Idiopathic retinal vasculitis Sarcoidosis

White-dot syndromes Vogt–Koyanagi–Harada syndrome AIDS

Syphilis

Serpiginous choroidopathy ASSOCIATED SYMPTOMS AND SIGNS Sinusitis – Wegener’s disease

found to have a slight decrease in visual acuity in the left eye and bilateral mild vitritis. Over the next 3 months her vision decreased in both eyes, and she was referred to the National Eye Institute. She had a history of type II diabetes mellitus controlled with oral hypoglycemic agents, and of rheumatic fever as a child. She also complained of weight loss and unsteady gait. She lived in a wooded area in Glen Falls, New York.

On examination, visual acuity was 20/50 in the right eye and 20/125 in the left. Anterior segment examination was normal, but there were 2+ vitreous cells and 1+ vitreous haze in both

57

Part 2 • Diagnosis

Chapter 4 Development of a Differential Diagnosis

Figure 4-2.  Fundus photograph showing yellow subretinal infiltrates, retinal hemorrhage, and retinal edema in eye with 20/125 visual acuity and moderate vitritis.

eyes. Funduscopic examination revealed punctate yellow subretinal infiltrates in both eyes and retinal hemorrhage and edema in the left eye (Fig. 4-2). Physical examination revealed ataxia.

Again, this patient’s condition presents difficulty in diagnosis, but with the approach detailed in Case 4-1 a differential diagnosis can be readily developed. The disease is chronic and the inflammation nongranulomatous. It is a bilateral disease and is classified as a multifocal retinitis. Therefore the patient is classified as having a chronic, nongranulomatous, bilateral, multifocal retinitis. She is an elderly white woman, and the history of living in a wooded area suggests a demographic susceptibility to Lyme disease. Her symptom of weight loss suggests the possibility of an underlying malignancy, malnutrition, or possible gastrointestinal disease, and the unsteady gait alerts the clinician to the possibility of neurologic disease. The diagnoses generated by this classification are shown in Box 4-10. As you can see, the most frequently listed diagnoses include sarcoidosis, infectious diseases, and the masquerade syndromes, most notably intraocular lymphoma.

Our first concern was that the patient had an underlying malignancy. Systemic evaluation was unrewarding, and a vitrectomy showed no malignant cells. However, two measurements of serum angiotensin-converting enzyme levels were elevated at 81 U/L and 101 U/L (normal range 8–52 U/L), and a bronchoscopy confirmed the diagnosis of sarcoidosis.

We hope that this chapter will provide the clinician with a pragmatic approach to generating a differential diagnosis. This

Box 4-10  Lists of diagnoses generated for Case 4-2

Chronic, nongranulomatous, bilateral, multifocal retinitis in an elderly white woman

CHRONIC UVEITIS

Juvenile rheumatoid arthritis Birdshot choroidopathy Serpiginous choroidopathy Tuberculous uveitis

Postsurgical uveitis (Propionibacterium acnes, fungal) Intraocular lymphoma

Sympathetic ophthalmia Multifocal choroiditis Sarcoidosis

Intermediate uveitis/pars planitis GRANULOMATOUS INFLAMMATION IN THE EYE Sarcoidosis

Sympathetic ophthalmia

Uveitis associated with multiple sclerosis Lens-induced uveitis

Intraocular foreign body Vogt–Koyanagi–Harada syndrome Syphilis

Tuberculosis

Other infectious agents MULTIFOCAL RETINITIS Syphilis

Herpes simplex virus Cytomegalovirus Sarcoidosis Masquerade syndromes

Candida

Meningococcus AGE >65 YR

Idiopathic anterior uveitis Idiopathic intermediate uveitis Idiopathic retinal vasculitis Serpiginous choroidopathy Masquerade syndromes Sarcoidosis

DEMOGRAPHIC CONSIDERATIONS

Patient lives in an area endemic for Lyme disease

will then permit the ophthalmologist to order the appropriate tests to discern among the most likely possibilities. As you will see in Chapter 5, the alternative shotgun approach of indiscriminately ordering every diagnostic test in the book may be both expensive and misleading.

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3.Jabs DA, Nussenblatt RB, Rosenbaum JT. Standardization of Uveitis Nomenclature (SUN) Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthlamol 2005; 140: 509–516.

4.Bloch-Michel E, Nussenblatt RB. International Uveitis Study Group recommendations for the evaluation of intraocular inflammatory disease. Am J Ophthalmol 1987; 103: 234–235.