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Localization of igm in plasma cells in the iris of a patient with iridocyclitis and juvenile rheumatoid arthritis.

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BRIEF REPORT
LOCALIZATION OF IgM IN PLASMA CELLS IN THE IRIS OF A
PATIENT WITH IRIDOCYCLITIS AND JUVENILE RHEUMATOID
ARTHRITIS
WILLIAM A. GODFREY, CAROL B. LINDSLEY, an d FRANCIS E. CUPPAGE
The pathophysiology of the iridocyclitis associated with juvenile rheumatoid arthritis is poorly understood. Clinically, the process has been well documented
by slit lamp biomicroscopy. The course, frequently
asymptomatic, is that of a low-grade chronic iridocyclitis (anterior segment inflammation) with little grossly
visible in the way of injection of the conjunctival episcleral or scleral vessels (1-5). Iridocyclitis is closely associated with pauciarticular (oligoarticular) juvenile
rheumatoid arthritis and with the presence of antinuclear antibodies (ANA) in serum (7-9).
We wish to present the histopathologic, immunofluorescent, and electron microscopic findings in the iris
of a child with iridocyclitis associated with monarticular
juvenile rheumatoid arthritis.
Case report. A 4-year-old black girl had an upper respiratory infection and a red eye for 2 weeks.
There was no history of trauma or musculoskeletal
complaints. The family history contained no known eye
disease.
On physical examination the left sclera was
mildly injected and there was a slight left ptosis. Corrected visual acuity was 20/20 in the right eye and light
perception only was observed in the left eye. Slit lamp
examination of the left eye revealed a corneal haze with
band keratopathy of the cornea seen as a peripheral
subepithelial infiltration at 4 to 5, and 7 to 8 o’clock at
From the Departments of Ophthalmology, Pediatrics, and
Pathology, University of Kansas Medical Center, Kansas City, Kansas.
William A. Godfrey, MD: Associate Professor of Ophthalmology; Carol B. Lindsley, MD: Assistant Professor of Pediatrics;
Francis E. Cuppage, MD: Professor of Pathology.
Address reprint requests 10 William A. Godfrey, MD, Department of Ophthalmology, University of Kansas Medical Center,
39th and Rainbow Blvd., Kansas City, Kansas 66103.
Submitted for publication November 4, 1980 accepted in revised form February 2, 1981.
Arthritis and Rheumatism, Vol. 24, No. 9 (September 1981)
the limbus and extending 2 mm into the cornea. The anterior chamber contained 3+ cells (40 cells per field with
biomicroscope beam 1 mm x 3 mm through anterior
chamber) and 3+ flare (iris and lens detail hazy). The
pupil was irregular with extensive posterior synechiae
present. The cornea was slightly edematous with a few
poorly defined keratitic precipitates on the lower central
endothelial surface. The left lens was cloudy with a far
advanced posterior subcapsular cataract. With dilation
there was partial visualization of the vitreous and poor
detail of the peripheral fundus with indirect opthalmoscopy. The posterior pole details remained obscured
though no gross abnormalities were visible and a red reflex was clearly seen. The right eye was normal.
Laboratory tests revealed the following: white
blood cells-7200/mrn3; hemoglobin-I I .5 grams/dl;
erythrocyte sedimentation rate ( E S R W mm/hr; quantitative immunoglobulins; IgG-1450
mg/dl (normal
for age, 365-1516 mg/dl); IgM-350 mg/dl (normal for
age, 60-250 mg/dl); IgA-150 mg/dl (normal for age,
3 1-201 mg/dl). Antinuclear antibodies (ANA) were
present in the serum in a 1 : 160 titer with a homogeneous pattern. Serum titers for histoplasmosis, toxoplasmosis, and cytomegalovirus were negative. Chest radiograph was within normal limits.
Treatment of the left eye with increasingly frequent topical dexamethasone 0.1% and atropine 1% produced mild response in the cells and flare, but the synechiae continued to worsen. Seven months later because
of chronic intraocular inflammatory disease and development of impending total seclusion of the pupil with
secondary acute angle closure glaucoma, the patient underwent a sector iridectomy of the left eye. The iris was
submitted for light microscopy, electron microscopy,
and immunofluorescence.
The posterior fundus was not visible postoperatively because of posterior subcapsular cataract
1196
BRIEF REPORTS
changes. The vitreous viewed around the cataract was
clear and peripheral retina appeared normal.
One month postoperatively she developed pain
in her right knee associated with swelling, warmth,
tenderness, and limitation of motion, The synovial fluid
was cloudy with poor much clot. Cultures were negative for bacterial and fungal growth; no organisms were
seen on Gram stain. Erythrocyte sedimentation rate was
25 mm/hr, and ANA was again positive at 1 : 160 titer.
Type specific staining showed the antinuclear antibody
to involve both the IgM and IgG classes. The diagnosis
of juvenile rheumatoid arthritis with associated chronic
iridocyclitis was made. Radiographs of the knees
showed normal findings except for soft tissue swelling;
histocompatibility antigen typing revealed A2, B7, and
Bw16. No immune complexes were detected by a Clq
binding assay (10). Total hemolytic complement and
DNA antibody determinations were normal.
The patient was treated with aspirin, I00 mg/kg/
day, to which she responded over a period of 3 weeks.
She continued to have intermittent stiffness and swell-
Figure 2. Electron microscopy photomicrograph of a stromal plasma
cell within a cytoplasm containing typical abundant endoplasmic reticulum with fine granular contents. Lead citrate and uranyl acetate
stained (X 11,OOO).
Figure 1. Light microscopy photomicrograph of the ins stroma containing a moderate number of plasma cells and pigment cells. Toluidine blue stained I p section (X 900).
ing over the next 6-8 months but maintained full range
of motion on the aspirin therapy. Approximately 1 year
after onset of her arthritis, the aspirin was discontinued
without a recurrence of joint symptoms during the subsequent 15 months.
Materials and methods. The segment of iris prepared for light and electron microscopy was fixed in 1%
glutaraldehyde and 4% formaldehyde, dehydrated in
ethyl alcohol, and embedded in epon-araldite. For light
microscopy 1p sections were stained with toluidine blue
and photographed in a Zeiss Ultraphot Photomicroscope. For electron microscopy 100 mp sections were
stained with lead citrate and uranyl acetate and photographed in a JEOL 100 S electron microscope. The segment of iris prepared for immunofluorescence was frozen in liquid nitrogen, sectioned at 5p with a cryostat,
and stained with fluorosceinated anti-human IgG, IgA,
and IgM and c3*
was photographed in a
ZeiSS Fluorescent Photomicroscope using epi-illumination.
BRIEF REPORTS
1197
Results. Light microscopy revealed scattered
plasma cells and pigment cells within the iris stroma
(Figure 1). Occasional plasma cells contained a granular cytoplasm. Polymorphonuclear leukocytes were not
identified. By electron microscopy the plasma cells’
cytoplasm contained either prominent endoplasmic reticulum with finely granular content (Figure 2) or numerous granules within the endoplasmic reticulum
suggestive of Russell bodies (Figure 3). Pigment cells
and occasional fibroblasts were present. Immunofluorescence demonstrated IgM within the cytoplasm of
scattered stromal cells (Figure 4). IgG, IgA, and complement were not demonstrated.
Discussion. The pathogenesis of iridocyclitis associated with juvenile rheumatoid arthritis is poorly understood. Few histopathologic studies exist that are useful in differentiating it from other forms of childhood
iridocyclitis (11). In addition, the hazards of ocular
biopsy procedures or surgery on the inflamed eye make
few specimens available. Specimens that do become
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Figure 4. Imrnunofluorescence photomicrograph depicting cytoplasmic localization of IgM within scattered cells of the iris stroma (x
350).
Figure 3. Electron microscopy photomicrograph of a stromal plasma
cell (P) containing dense granules (G) within the endoplasmic reticulum. An adjacent pigment cell (pig) is present. F = fibroblast; c =
collagen fibrils. Lead citrate and uranyl acetate stained ( X 9500).
available are often from late disease in which years of
chronic scarring and inflammatory alteration of tissue
structure result in an endstage histopathologic picture.
The different clinical types of juvenile rheumatoid arthritis with their widely varying risks for inflammatory eye disease have been generally recognized only
in recent years. Of the three major types of onset seen in
juvenile rheumatoid arthritis-systemic, polyarticular,
and pauciarticular-the highest risk for eye disease lies
in the pauciarticular group. These children have four or
fewer joints involved and usually mild arthritis. Additional risk is associated with the presence of antinuclear
antibodies in the serum. Eighty percent of children with
juvenile rheumatoid arthritis and iridocyclitis had positive tests for ANA in one large study (7). In this same
study the onset of iridocyclitis preceded the joint disease
in only 3% of patients, as was the case with our patient.
Change in the chronological order of the manifestations
is not considered to represent a significant difference in
the nature of the disease processes. Joint and eye are independent of each other with regard to their periods of
inflammatory activity and remission. Although chronic
iridocyclitis is frequently asymptomatic in young children, our patient’s advanced disease may have contributed to her acute intis that accompanied the chronic
disease.
BRIEF REPORTS
1198
The antinuclear antibodies present in children
with chronic iridocyclitis have been reported to be of
both IgG and IgM type, as was seen in this patient as
well. It is of interest that this patient showed mild elevation of serum IgM, which was also the type of immunoglobulin shown to be deposited in the ins. Whether the
serum elevation is a nonspecific response or is in some
way related to IgM deposition in the ins remains to be
delineated. The presence of numerous plasma cells,
some resembling Russell bodies, suggests that IgM is
being made locally by the plasma cells in response to an
unknown antigen.
REFERENCES
Smiley WK, May E, Bywaters EGL: Ocular presentations
of Still's disease and their treatment: iridocyclitis in Still's
disease; its complications and treatment. Ann Rheum Dis
161371-382, 1957
Kimura SJ, Hogan MJ, O'Connor GR, Epstein WV:
Uveitis and joint diseases: a review of 191 cases. Trans
Am Ophthal SOC,64:291-306, 1966
Key SN 111, Kimura SJ: Iridocyclitis associated with juvenile rheumatoid arthritis. Am J Ophthal80:425-429, 1975
4. Chylack LT Jr, Bienfang DC, Bellows AR, Stillman JS:
Ocular manifestations of juvenile rheumatoid arthritis.
Am J Ophthal79:1026-1033, 1975
5. Schaller J, Kupfer C, Wedgwood RJ: Iridocyclitis in juvenile rheumatoid arthritis. Pediatrics 44:92-100, 1975
6. Blegvad 0: Iridocyclitis and disease of the joints in children. Acta Ophthal 19:219-234, 1941
7. Schaller JC, Johnson GD, Holborow EJ, Ansell BM,
Smiley WC: The association of antinuclear antibodies
with the chronic iridocyclitis of juvenile rheumatoid arthritis (Still's disease). Arthritis Rheum 17:409416, 1974
8. Schaller J, Smiley WK, Ansell BM: Iridocyclitis of juvenile rheumatoid arthritis (JRA, Still's disease): a followup study of 76 patients (abstract). Arthritis Rheum
16:130-131, 1973
9. Kornreich HK, Drexley E, Hanson V: Antinuclear factors
in childhood rheumatic diseases. J Pediatr 69: 1039-1045,
1966
10. Lambert PH, Zubler RH: In Vitro Methods in Cell Mediated and Tumor Immunity. New York, Bloom & David,
Academic Press, 1976, p 565
11 Chylack LT, Dueker DK, Philaja D: Ocular manifestations of juvenile rheumatoid arthritis, Pathology, Fluorescein Iris Angiography and Patient Care. Edited by John J
Miller. 111. Mass, PSG Publishing Co, 1979, pp 149-163
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iris, patients, igm, iridocyclitis, arthritis, localization, juvenile, plasma, rheumatoid, cells
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