CLINICAL SCIENCES

Antineutrophil Cytoplasmic Antibody–Associated

Active Scleritis
Lani T. Hoang, MD; Lyndell L. Lim, MBBS, FRANZCO; Brian Vaillant, MD;
Dongseok Choi, PhD; James T. Rosenbaum, MD

Objective: To determine whether antineutrophil cyto-
plasmic antibody (ANCA) testing provides prognostic in-
formation in evaluating scleritis.
Methods: Retrospective medical record review of pa-
tients evaluated at a tertiary care center from January 1,
1995, to June 30, 2006, was performed to compare clini-
cal features, treatments, and associated systemic disease
in patients who test positive for ANCA vs patients whose
ANCA tests are negative.
significantly more ocular complications (21 of 14 or 86%
vs 20 of 64 or 31%; P ⬍.001), including keratopathy (5
of 14 or 36% vs 6 of 64 or 9%; P=.02), visual acuity of
20/50 or worse (8 of 14 or 57% vs 11 of 64 or 17%;
P=.001), and vascular pannus (3 of 14 or 21% vs 1 of 64
or 2%; P =.02). Aggressive therapy, such as chronic sys-
temic corticosteroids (9 of 14 or 64% vs 9 of 64 or 14%;
P⬍ .001) and alkylator therapy (8 of 14 or 57% vs 7 of
64 or 11%; P ⬍ .001), was more likely to be recom-
mended for patients who tested positive for ANCA.

Results: Among 78 patients identified, 14 tested posi-
tive for ANCA. Patients with positive ANCA test results
were more likely to have an associated systemic disor-
der (10 of 14 or 71%) than were patients who tested nega-
tive for ANCA (26 of 64 or 41%; P= .04), and the disor-
der was more likely to have been diagnosed as a result
of scleritis work-up (2 of 10 or 20% vs 19 of 26 or 73%;
P=.007). Patients with positive ANCA test results had
Conclusions: A substantial subset of patients with scle-
ritis are also positive for ANCA. These patients are more
likely to have severe ocular disease and undiagnosed pri-
mary vasculitic disease, thereby requiring more aggres-
sive therapy. An ANCA test may be useful in the evalu-
ation and treatment of patients with scleritis.
Arch Ophthalmol. 2008;126(5):651-655

Author Affiliations: Oregon
Health & Science University,
Portland (Drs Hoang, Lim,
Choi, and Rosenbaum), and
Department of Neuro-Oncology,
The University of Texas M. D.
Anderson Cancer Center,
Houston (Dr Vaillant).
S
CLERITIS IS A DESTRUCTIVE IN-
flammatory disorder of the
outer coating of the eye that
usually manifests as redness
and severe ocular pain. The
inflammation can spread to surrounding
structures of the eye, progress to ische-
mia and necrosis, and potentially cause se-
vere visual loss or blindness.1-3 Nearly half
of patients with scleritis have an associ-
ated immune-mediated condition, such as
rheumatoid arthritis (RA), relapsing poly-
chondritis, inflammatory bowel disease, or
primary vasculitis.2
Among patients with an associated dis-
ease, most patients seek treatment for sys-
temic disease before the onset of scleri-
tis.2 However, patients with a primary
vasculitic disease, such as Wegener granu-
lomatosis (WG) or polyarteritis nodosa
(PAN), have a more aggressive form of
scleritis and are more likely to first seek
treatment for scleritis.2,3 If left untreated,
primary vasculitic disease leads to multi-
organ failure and is potentially fatal.3,4 The
combination of corticosteroid and cyclo-
phosphamide treatment has been shown
to improve survival in patients with WG
and PAN.3,4 Therefore, early diagnosis and
initiation of treatment are critical for pa-
tients with scleritis associated with pri-
mary vasculitic diseases.
Diagnosing systemic vasculitides may
be difficult and often relies on a combi-
nation of clinical, pathological, and im-
munological criteria. In clinical settings,
when patients have active inflammation
and high pretest probability, the detec-
tion of antineutrophil cytoplasmic anti-
bodies (ANCA) serves as a useful clinical
marker for vasculitis.5,6 With an indirect
immunofluorescence assay, ANCA stains
in 2 major patterns. The cytoplasmic pat-
tern (c-ANCA) detects a neutrophil serine
proteinase and exhibits a diffuse staining
throughout the cytoplasm. Alternatively,
the perinuclear staining pattern (p-ANCA)
is exhibited when antibodies detect lyso-
somal enzymes such as myeloperoxi-
dase. Typically, c-ANCA has been associ-
ated with WG, and p-ANCA has been
linked to renal vasculitis and micro-

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 scopic polyarteritis.2-7 However, ANCA testing is not de-
finitive for systemic vasculitis, and there is overlap in clini-
cal phenotypes among patients with p-ANCA or c-ANCA
as well as patients negative for ANCA.
Although ANCA testing plays a critical role in the
evaluation of vasculitides, its clinical significance in pa-
tients with scleritis has not been clearly established. A
previous study reviewed the clinical features of and treat-
ment for scleritis and gave insight into the value of ANCA
testing.1 The study found a subset of patients with scle-
ritis who tested positive for c-ANCA but had no evi-
dence of an associated systemic disease.1 These patients
had difficult-to-control scleritis, suggesting c-ANCA may
be an independent prognostic marker.
To investigate the prognostic significance of ANCA test-
ing in scleritis, we evaluated patients who tested negative
for ANCA and compared this group with patients who tested
positive for p-ANCA or c-ANCA. We also examined ocu-
lar complications, treatments, associated diseases, and tim-
ing of the systemic diagnosis relative to scleritis.
METHODS
Medical records from all patients with scleritis evaluated at the
Inflammatory Eye Disease Clinic, Casey Eye Institute, Oregon
Health & Science University between January 1, 1995, and June
30, 2006, were retrospectively reviewed. Patients seen before
1995 were excluded because ANCA screening was not rou-
tinely administered. The study protocol was reviewed and ap-
proved by the Oregon Health & Science University Institu-
tional Review Board.
Scleritis was diagnosed based on characteristic clinical find-
ings of inflammation and edema affecting the scleral tissues,
with involvement of the superficial and deep episcleral vascu-
lar plexus.8 Posterior scleritis was confirmed by B-scan ultra-
sonography, computed tomography, and/or magnetic reso-
nance imaging of the orbits.7,8 Scleritis was classified as diffuse
anterior, nodular, necrotizing, scleromalacia perforans, or pos-
terior based on the system devised by Watson and Hayreh.8
Patient data, including age, sex, eye involvement, and fol-
low-up period, were recorded. Ocular complications included
visual impairment, scleral thinning, corneal involvement, uve-
itis, elevated intraocular pressure, and posterior segment in-
volvement. Visual impairment was categorized as visual acu-
ity of 20/50 or worse and visual acuity of 20/200 or worse. Scleral
thinning was defined as degeneration of the sclera leading to
loss of scleral rigidity.7 Corneal involvement included any signs
of corneal infiltrates, corneal thinning, stromal keratitis, and
corneal ulceration.7 Uveitis was classified according to the guide-
lines from the Standardization of Uveitis Nomenclature Work-
ing Group.9 Elevated intraocular pressure was defined as greater
than 21 mm Hg. Cystoid macular edema was defined by clini-
cal and angiographic criteria. Posterior segment involvement
included any findings of optic nerve edema, serous retinal de-
tachment, or choroidal folds.7 Because the percentages of com-
plications found are potentially affected by the duration of follow-
up, we further analyzed the rate at which these outcomes
occurred.10
Associated systemic disease was diagnosed based on com-
patible medical history, physical findings, imaging, laboratory
results, and confirmation by an appropriate specialist. All pa-
tients were evaluated by a rheumatologist. At the initial evalu-
ation of scleritis, nearly all patients were routinely screened for
ANCA immunofluorescence to determine the presence of
c-ANCA or p-ANCA. Results of the screening were confirmed
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by radioimmunoassay for the presence of antibodies to serine
proteinase 3 or myeloperoxidase. All tests ordered from Janu-
ary 1, 1995, through June 30, 2006, were performed by ARUP
Laboratories (Salt Lake City, Utah) using indirect fluorescent
antibody/multianalyte fluorescent detection. Patients with ex-
clusively infectious causes of scleritis or episcleritis were not
screened for ANCA and were excluded from the study. Pa-
tients with inactive scleritis were considered to have low pre-
test probability and were also excluded. Patients who had a
clearly established connective tissue disorder such as RA and
who had no evidence of a second associated condition were not
screened for ANCA. Other routine tests included urine analy-
sis, serum creatinine, and fluorescent treponemal antibody ab-
sorption. Additional tests such as rheumatoid factor, anti-
nuclear antibody, erythrocyte sedimentation rate, C-reactive
protein, and chest radiography were performed if deemed ap-
propriate by a rheumatologist, based on the patient’s history
and physical examination.
Treatment was based on type of scleritis, severity of dis-
ease, associated medical conditions, and patient preference. Drug
dosage and tapering were determined by clinical response and
tolerance of the medication. For most patients with mild an-
terior scleritis, an oral nonsteroidal anti-inflammatory drug was
the first-line treatment. For complicated, refractory, necrotiz-
ing, or posterior scleritis, systemic corticosteroid treatment (oral
or intravenous) was initiated. Chronic corticosteroid therapy
was defined as use for more than 6 months over a 1-year pe-
riod. Indications for the use of immunosuppressive drugs/
steroid-sparing agents included failure of scleritis to respond
to corticosteroid therapy, recurrence of scleritis, corticoste-
roid toxicity, the physician’s judgment that a corticosteroid-
sparing drug was indicated, or presence of active associated sys-
temic disease. Corticosteroid-sparing medications included
antimetabolite therapy (azathioprine, methotrexate sodium, and
mycophenolate mofetil), alkylator therapy (chlorambucil and
cyclophosphamide), and others (cyclosporine, infliximab, ri-
tuximab, and intravenous immunoglobulin).
Clinical characteristics, treatments, and associated medi-
cal conditions were compared between patients positive for
ANCA and patients negative for ANCA and between patients
positive for c-ANCA and p-ANCA. Distributions of categori-
cal variables were compared using the Fisher exact test with
exact procedures for the calculation of significance. Continu-
ous variables were compared using the 2-tailed t test. Nominal
P values were used for all comparisons, and P⬍.05 was con-
sidered statistically significant.
RESULTS
Of 101 patients with scleritis, 78 met the inclusion cri-
teria, and 23 were excluded because they had inactive
disease, episcleritis exclusively, or infectious scleritis. Of
the 78 patients included, 14 patients (18%) tested posi-
tive for ANCA, and 64 were considered ANCA negative,
including 52 patients with a negative ANCA test result
and 12 patients with clearly established RA without evi-
dence of a second immune-mediated disorder. Demo-
graphic characteristics and scleritis classifications were
not significantly different between the 2 study groups
(Table 1). Most patients in both subgroups were women
aged 40 to 50 years. The mean follow-up for ANCA-
positive patients (22 months; range, 0-86 months) was
longer than that for ANCA-negative patients (9 months;
range, 0-63 months), but this difference was not statis-
tically significant (P=.09). Anterior diffuse scleritis was
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 Table 1. Clinical Comparisons for Patients With Positive Table 2. Onset of Scleritis Complications
vs Negative ANCA Test Results
Complication Developed
Negative Positive P During Follow-up, %
Characteristic for ANCA a for ANCA a Value b
Negative Positive
Demographic characteristic Complication for ANCA for ANCA
No. of patients 64 14
Mean age at diagnosis, y 48 55 .12 Visual acuity ⱕ20/50 32 8
Women 45 (70) 10 (70) ⬎.99 Visual acuity ⱕ20/200 4 8
Mean duration of follow-up 9 (0-63) 22 (0-86) .09 Scleral thinning 28 17
(range), mo Keratopathy 16 17
Bilateral eye involvement 25 (39) 9 (64) .14 Vascular pannus 4 8
Scleritis type Uveitis 12 4
Diffuse anterior 35 (55) 10 (71) .37 Elevated intraocular pressure 0 0
Nodular anterior 22 (34) 2 (14) .21 Cystoid macular edema 0 0
Scleromalacia perforans 2 (3) 0 ⬎.99 Posterior complication 4 4
Necrotizing 1 (2) 0 ⬎.99
Posterior 4 (6) 2 (14) .29 Abbreviation: ANCA, antineutrophil cytoplasmic antibodies.
Scleritis complications
Ocular complications 20 (31) 12 (86) ⬍.001
Visual acuity ⱕ20/50 11 (17) 8 (57) .001
Visual acuity ⱕ20/200 5 (8) 3 (21) .39
curred more frequently in ANCA-positive patients than
Scleral thinning 17 (27) 6 (43) .33 in ANCA-negative patients (visual acuity ⱕ20/50, P=.001;
Keratopathy 6 (9) 5 (36) .02 visual acuity ⱕ20/200, P=.39) (Table 1). Keratopathy was
Vascular pannus 1 (2) 3 (21) .02 3 times more common in patients positive for ANCA than
Uveitis 4 (6) 3 (21) .11 it was in patients negative for ANCA (P=.02). Vascular
Elevated intraocular pressure 3 (5) 2 (7) .22 pannus also was seen more often in patients positive for
Cystoid macular edema 1 (2) 0 ⬎.99
ANCA (P=.02). In addition, more patients positive for
Posterior complication 2 (3) 1 (7) .45
Treatment ANCA had scleral thinning, uveitis, elevated intraocu-
Any systemic drug 63 (98) 14 (100) ⬎.99 lar pressure, and posterior segment complications, but
NSAID only 12 (19) 0 ⬎.99 the number of patients involved was too small for sta-
Corticosteroid, PO or IV 49 (77) 14 (100) .059 tistical analysis.
Chronic PO corticosteroids c 9 (14) 9 (64) ⬍.001 Outcomes are frequently affected by the duration of
Any steroid-sparing drug 31 (48) 13 (93) .002
follow-up.10 As noted above, the duration of follow-up
Antimetabolite d 29 (45) 9 (64) .25
Alkylator e 7 (11) 8 (57) ⬍.001
differed slightly between groups. To analyze the effect
Other f 9 (14) 2 (14) ⬎.99 of duration of follow-up, we calculated the rate of de-
Medical history velopment of specific outcomes in terms of patient years.
Any associated systemic disease 26 (41) 10 (71) .04 These rates did not differ significantly between patients
Diagnosed before scleritis 19/26 (73) 2/10 (20) .007 positive for ANCA and patients negative for ANCA
Any primary vasculitic disease 5 (8) 10 (71) ⬍.001 (Table 2).
Wegener granulomatosis 1 (1) 7 (50) ⬍.001
Generalized 0 3 (21) .004
Most patients were treated with a systemic medica-
Limited 1 (1) 4 (29) .003 tion, including nonsteroidal anti-inflammatory drugs
Polyarteritis nodosa 0 2 (14) .03 (Table 1). Most required systemic corticosteroids, but far
Rheumatoid arthritis 17 (26) 0 ⬍.001 more patients positive for ANCA were treated with long-
Psoriasis 2 (3) 0 ⬎.99 term corticosteroid therapy (P ⬍ .001). A steroid-
Cogan syndrome 2 (3) 1 (7) .45 sparing agent was also used with significantly greater fre-
Relapsing polychondritis 2 (3) 0 ⬎.99
quency among patients positive for ANCA (P=.002). This
Unidentified vasculitis 2 (3) 0 ⬎.99
difference is most striking when comparing the use of
Abbreviations: ANCA, antineutrophil cytoplasmic antibodies; alkylator therapy, 57% (8 of 14) of patients positive for
IV, intravenous; NSAID, nonsteroidal anti-inflammatory drug; PO, oral. ANCA required alkylator therapy compared with 11% (7
a Data are presented as number (percentage) unless otherwise indicated.
b P value derived from Fisher exact test, except for P values for mean age
of 64) of patients negative for ANCA (P ⬍.001).
at diagnosis and mean duration of follow-up which were derived from t test.
Patients positive for ANCA also had systemic disease
c Chronic corticosteroids defined as treatment lasting more than 6 mo over significantly more often than patients negative for ANCA
1-y period. (P=.04); in particular, ANCA-positive scleritis was as-
d Includes azathioprine, methotrexate sodium, and mycophenolate mofetil.
e Includes chlorambucil and cyclophosphamide. sociated with a primary systemic vasculitis (P ⬍ .001)
f Includes cyclosporine, infliximab, and rituximab. (Table 1). The most common primary systemic vasculi-
tis associated with ANCA was WG, which was seen in 7
patients (50%), followed by PAN, which was seen in 2
patients (14%). Among patients with WG positive for
the most common type in both groups. Bilateral eye in- ANCA, 3 had generalized WG and 4 had limited WG.
volvement was present in approximately half the patients. Limited WG was also diagnosed in 1 patient with a nega-
Patients who tested positive for ANCA experienced tive ANCA test.
more complications than patients who tested negative for Scleritis was more likely to be the presenting feature
ANCA (86% vs 31%; P ⬍.001). Visual impairment oc- of an associated systemic disease in patients positive for

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 ocular pressure. Visual impairment was present in all pa-
Table 3. Comparison of Patients With c-ANCA tients positive for c-ANCA and 5 of 7 patients positive
and p-ANCA Scleritis for p-ANCA. Nearly all patients in each subgroup re-
quired a steroid-sparing agent in addition to an oral cor-
Characteristic c-ANCA a p-ANCA a
ticosteroid. The use of alkylators and antimetabolites was
Total 7 7 similar in both subgroups. Association with a primary
Demographic characteristic vasculitis was also similar in both groups. Among pa-
Mean age at diagnosis, y 46 64
Women 5 5
tients positive for c-ANCA, 5 had WG, and 1 had Cogan
Mean duration of follow-up, mo 14 28 syndrome. Among patients positive for p-ANCA, 2 had
Bilateral eye involvement 4 5 WG and 2 had PAN.
Scleritis type
Diffuse anterior 3 7
Nodular anterior 2 0 COMMENT
Scleromalacia perforans 0 0
Necrotizing 0 0
Posterior 2 0 We examined the prognostic value of ANCA testing in
Scleritis complications scleritis. Our results indicated that ANCA testing iden-
Ocular complications 7 5 tifies a subset of patients with scleritis who are more likely
Visual impairment 7 5 to have severe ocular disease, require multiple immuno-
Scleral thinning 4 2 suppressive therapies, and have an underlying vasculi-
Keratopathy 1 4
tis diagnosed as a result of their scleritis. We also inves-
Vascular pannus 2 1
Uveitis 3 0
tigated the difference between p-ANCA scleritis and
Elevated intraocular pressure 1 1 c-ANCA scleritis. Patients positive for p-ANCA had dif-
Posterior complication 1 0 fuse anterior-type scleritis, whereas patients positive for
Treatment c-ANCA had heterogeneous types of scleritis; other-
Oral corticosteroids 7 7 wise, there was no striking distinction between c-ANCA
Antimetabolite 5 4 and p-ANCA scleritis. Because there was a small num-
Alkylator 4 4
Other 2 0
ber of patients in both subgroups, statistical analysis
Medical history was limited, and larger studies are required for future
Any associated systemic disease 6 4 investigations.
Wegner granulomatosis 5 2 Most patients with scleritis positive for ANCA pre-
Generalized 2 1 sented de novo without any history of an immune-
Limited 3 1 mediated condition. With further work-up, most of these
Polyarteritis nodosa 0 2
patients were found to have an underlying primary vas-
Cogan syndrome 1 0
culitic disease, most commonly WG. This correlates with
Abbreviations: c-ANCA, cytoplasmic pattern antineutrophil cytoplasmic the results found in a previous study, which showed that
antibodies; p-ANCA, perinuclear pattern antineutrophil cytoplasmic patients with a primary vasculitis are more likely to be
antibodies.
a Data are presented as number of patients unless otherwise indicated.
identified as a consequence of their scleritis.2 Because of
the potential for life-threatening complications, all pa-
tients with scleritis should have an ANCA test per-
formed, and those who test positive should be thor-
ANCA. Of 26 patients negative for ANCA with an asso- oughly evaluated for an underlying systemic vasculitis.
ciated disease, 19 (73%) presented with a known his- In this respect, we use the ANCA test in evaluating pa-
tory of the concurrent systemic disease. In contrast, 2 of tients with scleritis far differently than the rheumatoid
10 patients positive for ANCA with an underlying dis- factor or antinuclear antibody tests. We do not rou-
ease (20%) also had a pre-existing systemic diagnosis tinely screen patients with scleritis and a rheumatoid fac-
(P=.007). tor or antinuclear antibody because (1) scleritis is rarely
Within the ANCA-positive group, 7 (50%) were posi- the presenting manifestation for either RA or systemic
tive for c-ANCA, and 7 (50%) for p-ANCA (Table 3). lupus erythematosus; and (2) the specificities of rheu-
Patients positive for p-ANCA were significantly older at matoid factor and antinuclear antibody are such that a
initial treatment for scleritis than were patients positive diagnosis of either RA or systemic lupus erythematosus
for c-ANCA (mean age, 64 years [range, 49-84 years] vs cannot be established by laboratory values in the ab-
46 years [range, 30-61 years]; P = .01). All patients posi- sence of a compatible clinical presentation. In contrast,
tive for p-ANCA had anterior diffuse scleritis; con- a positive ANCA value can identify a population that is
versely, patients positive for c-ANCA had an assortment at increased risk for developing a systemic vasculitis,
of scleritis types, including 3 with diffuse, 2 with nodu- which has a substantially worse prognosis than other
lar, and 2 with posterior scleritis. Scleritis type corre- causes of scleritis. We do not recommend repeating the
lated with complications in both subgroups. In patients ANCA test once it is found to be negative unless the pa-
positive for p-ANCA, 2 had scleral thinning, and 4 had tient has developed additional evidence of systemic dis-
corneal complications; in comparison, 4 patients posi- ease, such as glomerulonephritis.11
tive for c-ANCA had scleral thinning, 3 had uveitis, 2 had Significantly more patients positive for ANCA had long-
corneal complications, 2 had vascular pannus, 1 had pos- term prescriptions for systemic corticosteroids and al-
terior segment complications, and 1 had elevated intra- kylator therapy than patients negative for ANCA. The

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 more aggressive treatment required for ANCA-positive
scleritis is confounded by the associated immune con-
dition in most patients positive for ANCA. As was shown
in previous studies, patients with scleritis and a primary
systemic vasculitis, such as WG or PAN, often require
systemic corticosteroids combined with alkylator therapy
for control of their eye disease.4 There may also be a bias
to initiate more aggressive treatment because of the poor
prognosis of patients with primary vasculitic diseases.
Patients positive for ANCA are at increased risk for de-
veloping visual impairment, keratopathy, and vascular pan-
nus. Corneal changes from corneal infiltrates, thinning, or
ulceration were the most common threat to vision. Al-
though patients with ANCA-positive scleritis had signifi-
cantly more ocular complications, a referral bias may ex-
ist because our clinic is part of a tertiary care medical center
and is likely to see more severe cases of scleritis.
As with all retrospective studies, our data must be in-
terpreted with caution. We found a significant subset of
patients with scleritis who were positive for ANCA. Al-
though ANCA test results may serve the physician as ad-
junct evidence for the diagnosis of vasculitis, these re-
sults must be viewed in the context of the patient’s clinical
picture and disease activity. Testing for ANCA is most
valuable in settings where there is a high pretest prob-
ability of vasculitis. We do not routinely screen patients
with inactive scleritis and no clinical evidence of an as-
sociated systemic disorder.
The ANCA test has become so closely associated with
the diagnosis of WG that some authorities use it as a di-
agnostic criterion. This would effectively bias any analy-
sis of the relationship between a test result positive for
ANCA and systemic disease. To avoid this bias, the di-
agnosis of limited WG was based on involvement of mul-
tiple organs other than the lungs or kidneys. Typical sites
of disease included the eyes, ears, sinuses, nose, or up-
per airway. These organs do not usually allow a histo-
logical confirmation of vasculitis. However, a positive
ANCA test was not a requirement to diagnose limited WG,
and the diagnosis was applied to patients who were nega-
tive for ANCA as well as patients who tested positive.12
A positive ANCA test result heralds an underlying pri-
mary systemic vasculitis that may not be clinically ap-
parent. Despite the limitations inherent in a retrospec-
tive study, we conclude that ANCA testing is a valuable
screening tool in evaluating patients with active scleri-
tis. A positive ANCA test result is a poor prognostic fac-
tor. Patients with ANCA-associated scleritis tend to have
more visual impairment, corneal complications, and vas-
cular pannus, and these patients often require com-
bined chronic systemic corticosteroid and alkylator
therapy for control of their eye disease. Further studies
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would be helpful in distinguishing any differences be-
tween patients with scleritis and positive p-ANCA test
results vs c-ANCA test results.
Submitted for Publication: June 1, 2007; final revision
received November 12, 2007; accepted November 19,
2007.
Correspondence: Lani T. Hoang, MD, Casey Eye Insti-
tute, Oregon Health & Science University, 2934 NW
Telshire Terr, Beaverton, OR 97006.
Author Contributions: Drs Hoang, Choi, and Rosenbaum
had full access to all the data in the study and take re-
sponsibility for the integrity of the data and the accu-
racy of the data analysis.
Financial Disclosure: None reported.
Funding/Support: This study was supported in part by
grant 5-P30-EY010572 from the National Institute of
Health, a Research to Prevent Blindness Senior Scien-
tific Investigator Award, and the Stan and Madelle Rosen-
feld Family Trust (Dr Rosenbaum).
Role of the Sponsor: The sponsors had no role in the de-
sign and conduct of the study; in the collection, analy-
sis, and interpretation of the data; or in the preparation,
review, or approval of the manuscript.
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