Crayola never manufactured a color to match these eyes. When Albert Martinez* first presented to our Cornea and External Disease Service, the 30-year-old had been suffering for five months with what had been diagnosed as “chronic bilateral conjunctivitis.”
In addition to redness and swelling, Mr. Martinez complained of significant pain, especially in his left eye and the left side of his face. Reportedly, the discomfort kept him from sleeping at night and prevented him from working.
Mr. Martinez had been evaluated by several ophthalmologists and treated with a variety of topical medications without clinical resolution. He was taking prednisolone acetate, which eased some of this discomfort but did not completely alleviate his symptoms. The pain remained constant and unrelenting and was associated with tearing and severe light sensitivity.
We Get a Look
On examination, his pinhole vision was 20/25 in his right eye and 20/80 in his left. His eyelids were ptotic from severe photophobia, and the left globe was exquisitely tender to palpation. The slit-lamp examination revealed conjunctival chemosis, injection and a deep violet hue to both sclera. Keratic precipitates lined both corneal endothelia, and punctate limbal keratitis was evident bilaterally. Anterior uveitis was present in the left eye, with 2+ cell and flare of the anterior chamber. The dilated exam was unremarkable and without signs of vasculitis, optic nerve edema or choroiditis.
Caption: The slit-lamp exam revealed conjunctival chemosis, injection and a deep violet hue in both the right (top) and left (bottom) eyes.
Although Mr. Martinez had originally denied any other medical problems, direct questioning elicited more information. In particular, he related recent hemoptysis and a hospitalization two months previously for pneumonia. In addition, he reported occasional low back and chest pain, and continued intermittent hemoptysis and epistaxis since his hospitalization. He denied having any fever, chills, rash, ulcers, dysuria, bowel irregularity or arthralgias. He also denied using intravenous drugs, having a sexually transmitted disease or even taking any recent trips.
Time to Run Tests
We requested a number of laboratory tests, including antinuclear antibody, rheumatoid factor, C-reactive protein, HLA-B27, angiotensin-converting enzyme and antineutrophilic cytoplasmic antibody (ANCA), as well as a chest x-ray and urinalysis. We continued his steroid and cycloplegic medication and began oral prednisone at a dose of 1 milligram per kilogram.
Many results were normal. However, Mr. Martinez had a positive c-ANCA titer of 1:80 and a high positive antiproteinase-3 level of 162 units. His rheumatoid factor was mildly elevated at 14.1, as was his complement C4, at 46 mg/dl. The urinalysis demonstrated trace protein, +1 gross blood and 3 to 5 red blood cells without RBC casts.
In light of these findings, we diagnosed Wegener’s granulomatosis, and Mr. Martinez was started on cyclophosphamide therapy at a dose of 150 mg/ day. We continued his prednisone at 70 mg/day; it was tapered slowly as symptoms improved. A nasal biopsy was taken; evaluation illustrated acute epithelial infiltrate and chronic vasculitis.
After six months of treatment, Mr. Martinez’s visual acuity had returned to normal and the slit-lamp exam revealed only bilateral mild residual scleral thinning without any ocular inflammation.
Results of repeat lab studies showed that Mr. Martinez’s c-ANCA and antiproteinase-3 levels had returned to normal, and his hematuria disappeared. His chest pain, hemoptysis and epistaxis all resolved, and his leukocyte counts remained above 4,000/microliter.
Watching for Wegener’s
In its complete form, Wegener’s is characterized by necrotizing granulomatous vasculitis of the upper and lower respiratory tracts combined with focal glomerulonephritis.
General symptoms. In most patients, the respiratory tract is affected first, and common presenting symptoms include paranasal sinus pain, epistaxis and mucosal ulceration. Distal pulmonary involvement manifests in 85 to 90 percent of cases. Renal involvement generally occurs later in the course of the disease, but it eventually dominates the clinical picture. Skin, cardiac and neurological findings also can be present.
Ophthalmic disease. This is the presenting feature in up to 16 percent of patients, and approximately 52 percent of those with Wegener’s eventually will experience ocular symptoms at some time during the course of their illness. Findings may be as benign as mild conjunctivitis or as dramatic as explosive proptosis with painful ophthalmoplegia and optic nerve compression. Some 8 percent of patients suffer loss of visual acuity; visual loss is generally bilateral.
Laboratory results. In 1985, the association between ANCAs and Wegener’s was first reported. At least two distinct classes of ANCAs have been described. Neutrophils that display diffuse granular fluorescence of cytoplasm after alcohol fixation are referred to as c-ANCA, while those with a perinuclear staining pattern are described as p-ANCA. The sensitivity of the c-ANCAs has been reported as high as 85 to 96 percent in patients with widespread disease and 80 percent in those with the limited variant. Antiproteinase-3 testing has a sensitivity of 85 percent; more important, it is a highly specific marker for Wegener’s.
Therapy and Comments
The standard therapy for Wegener’s is daily cyclophosphamide and corticosteroids. Cyclophosphamide generally is started at 2 mg/kg/day, but it can be increased to 3 to 5 mg/kg if warranted. Steroids are begun at 1 mg/kg/day, then tapered as symptoms resolve. Most patients remain on cyclophosphamide at least one year after clinical remission.
As illustrated in this case, a careful review of systems brought the diagnosis of Wegener’s to the forefront. Had a similar review been conducted before we saw Mr. Martinez, the diagnosis might have been pinned down earlier. Evaluation of ocular inflammatory disease often requires attention to subtle systemic complaints. As ophthalmologists, we will always concentrate on the ocular exam, but as physicians, we must remember the importance of a thorough systemic evaluation.
* Patient name is fictitious.
Drs. Maxwell and Chu are ophthalmologists at the New Jersey Medical School of the University of Medicine and Dentistry of New Jersey.