Epidemiology of Ocular Involvement in Autoimmune ...

Epidemiology of Ocular Involvement in Autoimmune Diseases COZIANA CIURTIN¹, VIORICA MĂDĂLINA COJOCARU², S. ARAMĂ¹, V. STOICA¹ ¹Department of Rheumatology, “I. Cantacuzino” Clinical Hospital, Bucharest, Romania ²Emergency Eye Hospital, Bucharest, Romania

The main objective of this study was to identify the prevalence of ocular manifestations in Romanian rheumatic patients admitted in a specialized rheumatology clinic since January 2006 till June 2007. The secondary outcome was the occurrence of adverse visual events associated with systemic therapy. Methods. Information regarding rheumatic and ocular diseases was extracted from medical records system available in “I. Cantacuzino” Clinical Hospital in Bucharest. The prevalence of ocular involvement reported passively by rheumatologists (retrospective descriptive study of 375 different cases of rheumatic patients) was compared with the literature data. Results. There were 29 cases of ocular manifestations. Ocular manifestation included keratoconjunctivitis sicca (KCS), anterior uveitis, conjunctivitis, retinal vasculitis and optic neuritis. Complications clearly related to steroid therapy were cataracts and glaucoma. One case with typical “bull’s eye” maculopathy due to Hydroxychloroquine treatment was detected. Conclusions. The main conclusion of our study is that the rheumatic patients need to be referred to an ophthalmologist for a precocious diagnosis of ocular involvement and an optimal treatment of eye manifestations. Key words: epidemiology, ocular manifestation, rheumatic diseases.

The rheumatic disorders are a heterogeneous collection of diseases, immunologically mediated, with a multitude of manifestations concerning different organs and systems. According to their involvement, they are grouped in arthritis, vasculitis and connective tissue diseases. American College of Rheumatology (ACR) has developed criteria for most of the rheumatic diseases in order to assist in diagnosis and research reporting [1][2]. Many of rheumatic diseases associate different major ophthalmic manifestations like conjunctivitis, KCS, uveitis, retinal vascular diseases or neuroophthalmic lesions. Each of these is most characteristically associated with some of the rheumatic disorders. Thus, KCS and scleritis are frequently associated with RA [3][4], acute anterior uveitis is most often seen with the seronegative spondyloarthropathies [5][6] and retinal vascular and neuro-ophthalmic lesions are often seen in SLE [7][8] or associated with vasculitis [9] [10]. MATERIAL AND METHODS

We undertook the first retrospective descriptive study of ocular manifestations in Romanian rheumatic patients. ROM. J. INTERN. MED., 2008, 46, 3, 243–247

The study was carried out at the Department of Rheumatology, “Ion Cantacuzino” Clinical Hospital in Bucharest. The hospital is a specialized referral centre that serves the whole country. Our study identified and characterized the prevalence of ophthalmic manifestations in rheumatic patients admitted in the clinic from January 2006 to June 2007. We reviewed the files of patients treated at the hospital for rheumatic diseases. The hospital medical records system was searched to identify patients who met the ACR criteria for RA, SLE, AS, scleroderma, reactive arthritis, psoriatic arthritis and vasculitis. In all, 375 eligible patients were found. The computerised database allowed access to details of characteristics of patients, medical history, history of the disease, age of diagnosis, history of laboratory findings and treatment, interdisciplinary examinations. The primary outcome was the prevalence of ocular manifestations associated with rheumatic diseases. The secondary outcome was the occurrence of adverse visual events associated with systemic therapy. We also compared our findings with data reported in the literature, because there has been no population-based study of the prevalence of ocular involvement in rheumatic diseases in Romania.

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groups. There were some patients identified in the initial database whose incomplete medical history or lost data excluded them from our study. Also, cases of ocular complications in conditions of no clear diagnosis of rheumatic diseases according to the accepted criteria were excluded. The repartition of different diseases indicated preponderance of RA and AS among our rheumatoid patients. This retrospective descriptive analysis included: 227 RA patients, 70 cases of AS, 37 cases with SLE, 19 patients with reactive arthritis, 12 patients with psoriatic arthritis, 3 cases of systemic vasculitis and 7 cases of scleroderma. The characteristics of the patient groups are shown in Table I. Table II gives the primary and secondary outcomes of our study.

The diagnosis of ophthalmologic involvement was accepted if established by the consultant ophthalmologist who had examined the patients. All statistical analyses were performed by Origin 5.0 programme. Descriptive statistics are presented as mean with standard deviation (SD) for continuous variables and percentage (%) for categorical variables. The most important descriptive values were expressed with 95% confidence intervals (95%CI) calculated using the exact binominal method (SEMSTAT downloadable software package). RESULTS

The complete medical records of 375 patients, who met the inclusion criteria, were reviewed in order to enlighten the characteristics of patient

Table I Characteristics of patient groups Parameter

RA

AS

Total (%) Sex (%) M F

227 (60.5%)

Age (years) at follow-up mean (SD) M F Disease duration (years) mean (SD) M F RF positive F% (M%) RF negative F%(M%) RF unspecified F%(M%) HLA B27 positive M% (F%) HLA B27 negative M% (F%) HLA B27 undetermined M% (F%)

Psoriatic arthritis 12 (3.2%)

SLE

Scleroderma

Vasculitis

70 (18.6%)

Reactive arthritis 19 (5.06%)

37 (9.9%)

7 (1.9%)

3 (0.8%)

10.13 89.87

50 50

63.15 36.85

33.33 66.67

2.71 97.29

0 100

0 100

52.9 (3.06) 50.7 (3.67)

36.2 (2.98) 36.2 (12.9)

27.5 (7.04) 28 (9.62)

56 (8.83) 39.6 (10.4)

44 36.5 (12.4)

0 41.8 (18)

0 53.3 (29)

6.7 (6.35) 7.12 (6.48)

8.6 (7.92) 6.2 (5.54)

0.67 (0.25) 0.78 (0.14)

7.12 (5.56) 2.56 (2.17)

6 11.3 (6.45)

0 9.56(3.7)

0 6.4 (4.2)

77.7 (94.4)

–

–

–

–

–

33.3 (0)

21.32 (1.26)

–

–

–

–

–

66.7 (0)

0.98 (4.34)

–

–

–

–

–

–

–

91.4 (94.3)

14.2 (8.3)

50 (0)

–

–

–

–

8.6 (5.7)

14.2 (16.7)

25 (25)

–

–

–

71.6 (75)

25 (75)

–

–

–

0 (0) –

RF = rheumatoid factor, SD = standard deviation, M = males, F = females, RA = rheumatoid arthritis, AS = ankylosing spondylitis, SLE = systemic lupus erythematosus

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Epidemiology of ocular involvement in autoimmune diseases Table II Primary and secondary outcomes Outcomes Conjunctivitis n (%), 95% CI Uveitis unilateral n (%), 95%CI bilateral n(%), 95%CI KCS n (%), 95%CI

RA

AS

Reactive arthritis

Psoriatic arthritis

SLE

Scleroderma

Vasculitis

– –

– –

2 (10.52) 0.013–0.33

– –

– –

– –

– –

– –

6 (8.57) 0.03– 0.17

1 (5.26) 0.0013–0.26

2 (16.6) 0.0208–0.484

1 (2.7) 0.0007– 0.14

– –

– –

– –

1 (1.42) 0.0003–0.076

– –

– –

– –

– –

– –

– –

– –

– –

2 (5.4) 0.006– 0.18

1 (14.28) 0.0036–0.58

– –

– –

– –

– –

– –

– –

– –

2 (5.4) 0.006– 0.18

– –

17 (24.3)

6 (31.5)

3 (25)

14 (37.8)

1 (14.28)

7 (3.09) 0.0125– 0.0624

Retinal vasculitis n (%), 95% CI

– –

Optical neuritis n (%), 95% CI

– –

Patients without ophthalmologic examination n (%)

Adverse visual therapy events n (%)

4 (10.8) 0.03–0.25

– –

93 (40.96)

– –

– –

0

2 (5.4) 0

0

8 (3.52)

0

0 0

n = number of patients, 95%CI = 95% confidence intervals, RA = rheumatoid arthritis, AS = ankylosing spondylitis, SLE = systemic lupus erythematosus

Of the 375 patients, 227 (60.5%) had RA, female patients outnumbered male patients by 8.87:1. Rheumatoid factor positive was associated with severe disease (the severity was assessed using Sharp radiographic index for every joint counted). Of the 227 patients with RA we found 7 cases (3.09%, 95%CI 1.25–6.24%) with KCS, all females, between 46 and 78 years old, with rheumatoid factor positive in all cases. We detected only one case with typical “bull’s eye” maculopathy, due to hydroxychloroquine treatment, with VA of 6/18(OS) and 6/24(OD) and no improvement after cessation of the drug.

Six of the 70 patients with AS (8.57%, 95%CI 3.21–17.7%) had developed sudden onset, unilateral anterior uveitis. All were male, HLAB27 typed and five were positive (83.3%, 95%CI 0.35–0.99). Only one male patient, HLA-B27 positive (1.42%, 95%CI 0.03–7.69), was diagnosed with alternating anterior uveitis. Three of the 19 patients (15.78%, 95%CI 3.38–39.5%) with reactive arthritis developed ocular involvement. One HLA-B27 positive male was diagnosed with unilateral anterior uveitis (5.26%, 95%CI 0.13–26%) and two males (HLA-

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B27 undetermined) with conjunctivitis (10.52%, 95%CI 1.3–33%). In psoriatic arthritis group two patients (16.6%, 95%CI 2.08–48.4%), both HLA-B27 positive, had developed anterior unilateral uveitis and axial disease. Uveitis complications were: two (28.57%) cataracts and one (14.28%) glaucoma in SA and one (8.33%) cataract in psoriatic arthritis group. Ocular involvement in SLE consisted in: two cases of KCS (5.4%, 95%CI 0.6–18%), one case of uveitis (2.7%, 95%CI 0.07–14%), four cases (10.8%, 95%CI 3–25%) of retinal vasculitis (two with antiphospholipid antibodies positive) and two cases (5.4%, 95%CI 0.6–18%) of optic neuritis (VA at last follow-up of 20/60 (OS), respectively 10/60 (OS)). One patient (33%, 95%CI 0.84–90.5%) with giant cell arteritis had unilateral visual loss attributable to the disease (after 5 years of systemic corticotherapy and immuno-suppressive treatment). One female patient (14.28%, 95%CI 0.36– 58%) with scleroderma developed KCS, 5 years after disease diagnosis. Complications clearly related to steroid therapy were: seven (3.08%) cataracts in RA and two (5.4%) cataracts in SLE. In our study, ocular conditions uncorrelated with diseases and treatments were: age related cataract (11 patients), glaucoma (2 patients) and traumatic ocular lesion with subsequent development of a traumatic cataract (1 patient). DISCUSSIONS

The low incidence of ocular involvement in our rheumatic patients makes clinical trials difficult to interpret. We tried to compare our findings with the literature data and to establish the particularities of the obtained results. Our study indicates that the most common ocular manifestations in rheumatic diseases are KCS and anterior uveitis, known from other studies as well [11]. In RA patients group our data conclude to the presence of 3.09% cases of KCS. This proportion compared well with a previous study [12] and was lower than other studies [3][4]. Different study

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groups, assessments, environmental and climate factors may account for these differences. In the group of SA patients we found an incidence of 10% of anterior uveitis, lower than others had observed [5][6]. All patients were men, 85.71% of them being HLA-B27 positive. For the group with reactive arthritis we found 15.78% cases of ocular involvement: anterior uveitis 5.26% and conjunctivitis 10.52% comparing to a mixture of conjunctivitis, uveitis and keratitis in about 20% of cases from literature data [5][6]. The proportion of patients with psoriatic arthritis and uveitis was of 16.6% and compared well with that found by Queiro et al. [13]. In SLE patients group we found an ocular involvement of 24.3%, with an incidence of KCS of 5.4%, lower than others have observed [14]. In our study, the most important side effects of the drugs used in rheumatic diseases treatment were: one case of “bull’s eye” maculopathy due to Hydroxychloroquine treatment and nine cases of cataracts related to steroid therapy. Some of our results evaluate a lower incidence of ocular manifestations in rheumatic diseases than in the literature data. It may be due to some limitations of our study. There were an important number of patients who had no ophthalmologic examination. The possibility that some of these individuals had developed asymptomatic or mild type of ocular involvement cannot be excluded. Rheumatic diseases are one of the usual expression of a multitude of manifestations concerning different organs and having different potential gravity and prognosis. An interdisciplinary approach to the rheumatic patient is necessary, being the only one that could provide a better understanding of the treatment needed for avoiding the irreversible damage of those chronic diseases. The practical clinical conclusion of our study is that the rheumatic patients need to be referred to an ophthalmologist for a precocious diagnosis of ocular involvement and an optimal treatment of eye manifestations.

Principalul obiectiv al studiului a fost de a identifica prevalenţa manifestărilor oculare în cadrul pacienţilor cu boli reumatice din Romania internaţi într-o clinică de profil în perioada ianuarie 2006–iunie 2007. Obiectivul secundar al studiului a fost determinarea incidenţei reacţiilor adverse oculare asociate cu terapia acestor boli.

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Metode. Informaţiile au fost extrase din cadrul fiselor medicale disponibile în sistemul computerizat al Clinicii de Medicina Internă şi Reumatologie din Spitalul „Dr. I. Cantacuzino” din Bucuresti. Prevalenţa manifestarilor oculare raportate în mod pasiv de către reumatologi (studiu retrospectiv a cuprins 375 de cazuri de afectiuni autoimune) a fost comparată cu cea din datele din literatură. Rezultate. Au fost depistate 29 de cazuri de afectare oculară. Principalele afecţiuni oculare decelate sunt keratoconjunctivita sicca, uveita, conjunctivita, vasculita retiniana, nevrita optica. Principalele determinări oculare secundare terapiei specifice acestor boli sunt dominate de cataractă şi glaucom. Nu a fost detectat decât un singur caz de maculopatie secundară tratamentului cu Hidroxiclorochină. Concluzii. Principala concluzie a studiului este aceea ca incidenţa raportată a afectării oculare în bolile autoimune este mai mică decât cea din literatura de specialitate probabil determinată de necesitatea, insuficient acoperită, a diagnosticului precoce oftalmologic în bolile autoimune pentru preîntâmpinarea fenomenului de subdiagnosticare. Corresponding author: Coziana Ciurtin, MD Clinic of Rheumatology, “I. Cantacuzino” Clinical Hospital, 5–7, I. Movila Str., Bucharest, Romania e-mail: [email protected]

REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14.

ARNETT F.C., EDWORTHY S.M., BLOCH D.A., MCSHANE D.J., FRIES J.F., COOPER N.S., The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis. Rheum., 1988, 31:315–24. TAN E.M., COHEN A.S., FRIES J.F. et al., The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis. Rheum., 1982; 25:1271–7. FUERST D.J., TANZER D.J., SMITH R.E., Rheumatoid diseases. Int. Ophthalmol. Clin., 1998; 38:47–80. HARPER S.L., FOSTER C.S., The ocular manifestations of rheumatoid disease. Int. Ophthalmol. Clin., 1998; 38:1–19. ROSENBAUM J.T., Acute anterior uveitis and spondyloarthropathies. Rheum. Dis. Clin. North Am., 1992; 18:143–51. BAÑARES A., HERNÁNDEZ-GARCÍA C., FERNÁNDEZ-GUTIÉRREZ B., JOVER J.A., Eye involvement in the spondyloarthropathies. Rheum. Dis. Clin. North Am., 1998; 24:771–84. NGUYEN Q.D., FOSTER C.S., Systemic lupus erythematosus and the eye. Int. Ophthalmol. Clin., 1998; 38:33–60. SOO M.P., CHOW S.K., TAN C.T., NADIOR N., YEAP S.S., HOH H.B., The spectrum of ocular involvement in patients with systemic lupus erythematosus without ocular symptoms. Lupus, 2000; 9:511–4. NEFF A.G., GREIFENSTEIN E.M., Giant cell arteritis update. Semin. Ophthalmol., 1999; 14:109–12. HAYREH S.S., PODHAJSKY P.A., ZIMMERMAN B., Ocular manifestations of giant cell arteritis. Am. J. Ophthalmol., 1998; 125:509–20. HAMIDEH F., PRETE P.E., Ophthalmologic manifestations of rheumatic diseases. Semin. Arthritis. Rheum., 2001 Feb., 30(4):217–41. BOGLIOLO A., MELA Q., PERPIGNANO L. et al., Ocular involvement in rheumatoid arthritis. Clin. Ter., 1993 Jan., 142(1):41–6. QUEIRO R., TORRE J.C., BELZUNEGUI J. et al., Clinical features and predictive factors in psoriatic arthritis-related uveitis. Semin. Arthritis. Rheum., 2002 Feb., 31(4):264–70. GILBOE I.M., KVIEN T.K., UHLIG T., HUSBY G., Sicca symptoms and secondary Sjogren’s syndrome in systemic lupus erythematosus: comparison with rheumatoid arthritis and correlation with disease variables. Ann. Rheum. Dis., 2001 Dec., 60(12):1103–9.

Received June 2, 2008

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