Clin Rheumatol (2013) 32:1387–1391 DOI 10.1007/s10067-013-2262-y
BRIEF REPORT
The uveitis and its relationship with disease activity and quality of life in Moroccan children with juvenile idiopathic arthritis M. Ezzahri & B. Amine & S. Rostom & Y. Rifay & D. Badri & N. Mawani & S. Gueddari & S. Shyen & M. Wabi & F. Moussa & R. Abouqal & B. Chkirate & N. Hajjaj-Hassouni
Received: 13 March 2013 / Revised: 19 March 2013 / Accepted: 7 April 2013 / Published online: 2 May 2013 # Clinical Rheumatology 2013
Abstract The aim of our study is to investigate ocular involvement in juvenile idiopathic arthritis (JIA) and its relationship with disease activity and quality of life in Moroccan patients who suffer from JIA. This is a cross-sectional study conducted between January and June 2012 which includes patients with juvenile idiopathic arthritis (n=30). All patients have undergone clinical and paraclinical assessment of JIA and a complete eye examination. Functional impairment is assessed by the Childhood Health Assessment Questionnaire while visual function is studied by the Effect of Youngsters’ Eyesight in Quality of Life instrument (EYE-Q). Quality of life is assessed using the Pediatric Quality of Life Inventory Version 4.0 (PedsQL 4.0). Four patients (13.33 %) have uveitis with a confidence interval between 3.4 and 30.7. Involvement is bilateral in three children (75 %). One patient M. Ezzahri (*) : B. Amine : S. Rostom : D. Badri : N. Mawani : S. Gueddari : S. Shyen : M. Wabi : F. Moussa : N. Hajjaj-Hassouni LIRPOS–URAC30, Service de rhumatologie, Hôpital El Ayachi, CHU Rabat-Salé, Université Mohammed V Souissi, Rabat, Morocco e-mail:
[email protected] B. Amine : R. Abouqal : N. Hajjaj-Hassouni LIRPOS–URAC30, Laboratoire de Biostatistique, Recherche Clinique et Epidémiologique (LBRCE), Faculté de Médecine et de Pharmacie, CHU Rabat-Salé, Université Mohammed V Souissi, Rabat, Morocco Y. Rifay Service d’Ophtalmologie A, Hôpital des Spécialités, CHU Rabat-Salé, Rabat, Morocco B. Chkirate Service de Pédiatrie IV, Hôpital d’Enfants, CHU Rabat-Salé, Rabat, Morocco
(25 %) has elevated intraocular pressure with loss of the right eye due to glaucoma. There is a strong but not significant relationship between uveitis and the number of awakenings (r=0.71, p=0.69) and morning stiffness (r=3.05, p=0, 21). This relationship is moderate with erythrocyte sedimentation rate (r = 0.48, p = 0.78) and C-reactive protein (r = 0.25, p=0.88). A strong but not significant association is found between the overall quality of life assessed by the PedsQL 4.0 and visual function assessed by EYE-Q in the uveitis group (r=−0.64, p=0.55). This study suggests that uveitis associated with JIA can present serious complications and could have a direct relationship with the activity of the JIA as well as with the quality of life of the patient. Keywords Disease activity . EYE-Q . Juvenile idiopathic arthritis . PedsQL 4.0 . Quality of life . Uveitis
Introduction The most frequent extra-articular manifestation of juvenile idiopathic arthritis (JIA) is an insidious asymptomatic anterior uveitis with a chronic disease course. Although its prognosis is improving, as a result of early recognition and prompt treatment, some children nonetheless become visually handicapped. A great challenge to ophthalmologists and pediatric rheumatologists is how to save the sight of these children [1, 2]. Despite the current guidelines for the screening program and administration of new immunosuppressive agents, JIAassociated uveitis continues to be a potentially blinding condition. Although some centers report very good visual
1388
outcome, some of the recent studies still show that up to 24 % of patients end up blind or with severe visual impairment [2–4]. Previous reports have suggested high prevalence rates ranging from 21 to 97 %. More recent reports have found a much lower prevalence of uveitis of about 13 %, and this may be due to the medications used systemically to treat the joint inflammation that may also tend to prevent the onset of uveitis [5]. It has been reported that although the activities of joint and eye inflammation may parallel each other, they are in fact more commonly independent. On the other hand, in some series, clinical and laboratory parameters show more active arthritis in patients with uveitis than in those without it [1]. In Morocco, a study evaluating the quality of life of children and adolescents patients with JIA suggests that JIA can have a significant adverse effect on the healthrelated quality of life (HRQOL) of Moroccan patients, particularly adolescents with polyarticular and systemic subtypes. Disease duration, disability score (Childhood Health Assessment Questionnaire (CHAQ)), and pain are the strongest determinants of poorer HRQOL [6]. In the absence of data about uveitis of juvenile idiopathic arthritis in Arabian countries and the Arab world, our objective is to investigate the prevalence of uveitis in children who suffer from juvenile idiopathic arthritis, its relationship with the activity of JIA, and its impact on quality of life. We also evaluate the individual impact of physical and visual disability on QOL in children with and without uveitis.
Subjects and methods Subjects Children who have JIA are recruited in consultations of El Ayachi Hospital and the Children Hospital between January and June 2012. Patient enrollment satisfies the following inclusion criteria: 1. The diagnosis of JIA according to the International League of Associations for Rheumatology classification [7]. 2. Age 8 to 18 years at time of study and age <16 years at time of JIA diagnosis. 3. Presence of parent or guardian to complete a written demographic questionnaire The exclusion criteria are as follows: major developmental disorders and other systemic disease associated with uveitis. Arthritis data collection included presence of arthritis, age at arthritis onset, distribution of joint involvement,
Clin Rheumatol (2013) 32:1387–1391
morning stiffness, awakenings, and patient visual analog scale (VAS). Assessment of physical function Physical function is measured by the Moroccan validated version CHAQ [8], which is an instrument for juvenile arthritis to evaluate functional disability. Uveitis-related data are based on complete ophthalmologic examination with the examination slit lamp, fundus examination, visual acuity, and intraocular pressure measurement. It searches the presence of uveitis, eye pain, and specific sequelae such as cataracts, glaucoma, and posterior synechiae. A history of past and current medication use, including name, class, duration of use, and mode of administration is obtained by self-report from the parent and by medical record review. Assessment of visual function To assess vision-related QOL, a new questionnaire (Effect of Youngsters’ Eyesight in Quality of Life instrument (EYE-Q)) has been developed. Relevant items have been selected from existing instruments and consulted pediatric rheumatologists, pediatric ophthalmology professionals (ophthalmologists, optometrists, clinical research technicians), and children with and without ocular disease [9]. Visual function is measured by the visual function questionnaire, EYE-Q—a patient-based self-report questionnaire consisting of 13 items that evaluate competence in performing daily tasks that rely on vision at school and home in children who are 8 to 18 years of age [9]. Additionally, recorded laboratory markers (most recent erythrocyte sedimentation rate test (ESR), C-reactive protein (CRP), antinuclear antibody test (ANA), rheumatoid factorrelated test) are noted. Quality of life assessment QOL has been defined by the World Health Organization as an individual’s perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards, and concerns [10]. Health-related QOL is measured by the Pediatric Quality of Life Inventory Version 4.0 (PedsQL 4.0)—an instrument for children and adolescents from 2 to 18 years of age and includes four core scales: (1) physical functioning (eight items), (2) emotional functioning (five items), (3) social functioning (five items), and (4) school functioning (five items). Each item is measured on a five-point scale, and scores range from 0 to 100 with higher scores indicating better QOL. This study uses the child and parent report forms.
Clin Rheumatol (2013) 32:1387–1391
1389
Results
Thirty patients are included. The mean age of patients is 11.33 ± 3.64, 40 % were females. The arthritis is oligoarticular in 30 % of cases, enthesitis and arthritis in 26.7 %, polyarticular in 16.7 %, and systemic arthritis in 23.3 %. Four patients (13.33 %) have uveitis associated with JIA with a confidence interval [3.4–30.7]. Involvement is bilateral in three children (75 %). Antinuclear antibody positivity is detected in two patients in the group with uveitis (50 %), with oligoarticular and polyarticular forms. Among the four patients with uveitis, three (75 %) develop cataracts, one (25 %) has elevated intraocular pressure with loss of the right eye due to glaucoma, one (25 %) has a band keratopathy, and one (25 %) has bilateral posterior synechiae.
PedsOL4
Demographic and disease characteristics
EYE-Q
Fig. 1 Correlation between the PedsQL and EYE-QL in the group without uveitis
Disease activity
Characteristics Mean age in years(SD) Female ANA(+) Arthritis characteristics Tender joints Swollen joints morning stiffness Median patient VAS (range) Median CHAQ (range) Uveitis characteristics Cataracts Glaucoma Band keratopathy Posterior synechiae Medication use NSAID Aspirin Prednisone Bolus of corticosteroids Methotrexate Quality of life Mean PedsQL (SD) Visual function Mean EYE-QL (SD) ND not done
Uveitis (N=4)
No uveitis (N=26)
12.75.(8.7) 1 (25 %) 2 (50 %)
11.11 (3.6) 11 (42.3) ND
3 (75 %) 2 (50 %) 3 (75 %) 35 (10–90) 0.75 (0–1.8)
15 (58 %) 6 (23 %) 11 (42 %) 20 (10–30) 0 (0–0.71)
3 (75 %) 1 (25 %)
0 0
1 (25 %) 1 (25 %)
0 0
2 (50 2 (50 2 (50 1 (25 1 (25
14 (56 %) 1 (4 %) 8 (33.3) 4 (15.4) 6 (23.1 %)
%) %) %) %) %)
72.10 (20.22)
78.25 (18.02)
1.71 (1.28)
1.23 (0.42)
There is a strong but not significant relationship between uveitis and the number of awakenings (r=0.71, p=0.69), morning stiffness (r=3.05, p=0.21), the number of tender joints (r = 1.75, p = 0.41), the number of swollen joints (r=2.95, p=0.22), the overall patient VAS (r=2.03, p=0.36), and the CHAQ (r=2.80, p=0.84). This relationship is moderate with ESR (r=0.48, p=0.78) and CRP (r=0.25, p=0.88). Medication use, including aspirin, oral and intravenous corticosteroid therapy, as well as DMARDS, is higher in uveitis group (Table 1).
PedsOL4
Table 1 Characteristics of patients with and without uveitis
EYE-Q
Fig. 2 Correlation between the PedsQL and EYE-QL in the uveitis group
1390
Quality of life and visual function A strong but not significant association is found between the overall quality of life assessed by the PedsQL 4.0 and visual function assessed by EYE-Q in the uveitis group (r=−0.64, p=0.55). This association remains lower in the group without uveitis (r=−0.20, p=0.26). Moreover, the relationship between visual function and the CHAQ is moderate in the uveitis group (r=0.27, p=0.82) but remains very low in the group without uveitis (r=0.04, p=0.84) (Figs. 1 and 2).
Discussion The prevalence figures for uveitis associated with JIA have been lower in recent reports than in the earlier literature. One possible explanation is that systemic medications used to treat the arthritis may tend to prevent the development of ocular inflammation [11, 12]. In our study, we find 13.33 % uveitis associated with JIA, confidence interval of [3.4–30.7], with one oligoarticular JIA, one polyarticular JIA, one systemic arthritis, and one enthesitis-related arthritis. Almost the same results are found in the study of Oren et al. when they report that the prevalence rate of uveitis in children with JIA is 13 %. Of 76 patients, six have oligoarticular JIA and one has polyarticular JIA [5]. Saurenmann et al. have examined a cohort of 1,081 patients who have been followed up at a single center for the prevalence and outcome of uveitis in JIA. They have found an overall prevalence of 13.1 % [2]. Better visual outcomes of children with JIA-associated uveitis have been reported in the literature. In our study, among the four patients with uveitis, three (75 %) have developed cataracts, one (25 %) has elevated intraocular pressure with loss of the right eye due to glaucoma, one (25 %) has a band keratopathy, and one (25 %) has bilateral posterior synechiae. In the study of Kotaniemi et al., 6 % of eyes of 163 patients ended with blindness [13]. Cataracts are among the most frequently observed ocular complications of JIA. New-onset cataracts in JIA-U patients have an estimated incidence of 0.04/eye-year and a reported prevalence between 9 and 80 % in children or uveitic eyes. However, their occurrence may be influenced by the duration of uveitis, degree of inflammation control, and concomitant topical corticosteroid use [13–15]. A study from Italy shows that 90.5 % of eyes have complications (64 % cataracts and 25 % glaucoma) [16]. Foster et al. reported that glaucoma complicates the course of JIA-associated uveitis in 42 % of 69 [17]. In a study of 148 children with uveitis from Bascom Palmer Eye Institute, relative risks for the development of band keratopathy, cataract, and posterior synechiae are the highest for the JIA subset of patients [18].
Clin Rheumatol (2013) 32:1387–1391
It has been reported that although the activities of joint and eye inflammation may parallel each other, they are in fact more commonly independent [1]. We find that the group with uveitis shows a higher score in number of awakenings, morning stiffness, number of tender joints, number of swollen joints, patient VAS, and CHAQ. This relationship is strong, but not significant, which can be related to the small size of the sample. In a series of 372 children with recently diagnosed JIA, clinical and laboratory parameters show more active arthritis in patients with uveitis than in those without it. They also report that clinical remissions of arthritis are significantly less frequent in patients with uveitis than in those without [19]. Our study shows a strong but not significant association between the overall quality of life assessed by the PedsQL 4.0 and visual function assessed by EYE-Q in the uveitis group. This association remains lower in the group without uveitis. Moreover, the relationship between visual function and the CHAQ is moderate in the uveitis group but remains very low in the group without uveitis. Angeles-Han et al. examine the association between the EYE-Q and the PedsQL on one hand and between the CHAQ on the other hand. In children with uveitis, there is a moderate correlation between visual function and quality of life, and there is no such correlation in the group without uveitis [9]. In conclusion, uveitis associated with JIA is a disease that threatens the visual prognosis of a child; hence, regular monitoring and adequate care can preserve visual function. In this study, a strong but not significant association is found between the presence of uveitis, activity parameters of JIA, visual function assessed by EYE-Q, and quality of life as assessed by the PedsQL 4.0. This can be related to the small size of the sample. Prospective studies on larger samples seem to be needed to confirm these results. Disclosures None.
References 1. Kaisu K, Anneli S, Anni K, Kimmo A (2003) Recent advances in uveitis of juvenile idiopathic arthritis. Surv Ophthalmol 48(5):489–502 2. Saurenmann RK, Levin AV, Feldman BM et al (2007) Prevalence, risk factors, and outcome of uveitis in juvenile idiopathic arthritis: a long-term follow-up study. Arthritis Rheum 56:647–657 3. Sabri K, Saurenmann RK, Silverman ED, Levin AV (2008) Course, complications, and outcome of juvenile arthritis-related uveitis. J AAPOS 12:539–545 4. Thorne JE, Woreta F, Kedhar SR et al (2007) Juvenile idiopathic arthritis-associated uveitis: incidence of ocular complications and visual acuity loss. Am J Ophthalmol 143:840–846
Clin Rheumatol (2013) 32:1387–1391 5. Oren B, Sehgal A, Simon JW, Lee J, Blocker RJ, Biglan AW, Zobal-Ratner J (2001) The prevalence of uveitis in juvenile rheumatoid arthritis. J AAPOS 5(1):2–4 6. Amine B, Rostom S, Benbouazza K, Abouqal R, Hajjaj-Hassouni N (2009) Health related quality of life survey about children and adolescents with juvenile idiopathic arthritis. Rheumatol Int 29:275–279 7. Petty RE, Southwood TR, Manners P et al (2004) International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol 31:390–392 8. Rostom S, Amine B, Bensabbah R, Chkirat B, Hajjaj-Hassouni RAN (2010) Psychometric properties evaluation of the childhood health assessment questionnaire (CHAQ) in Moroccan juvenile idiopathic arthritis. Rheumatol Int 30:879–885 9. Angeles-Han ST, Griffin KW, Lehman TJ, Rutledge JR, Lyman S, Nguyen JT, Harrison MJ (2010) The importance of visual function in the quality of life of children with uveitis. J AAPOS 14(2):163– 168 10. WHOQOL Group (1993) The development of the World Health Organization quality of life assessment instrument (the WHOQOL). Qual Life Res 2(2):153–159 11. Boone MI, Moore TL, Cruz OA (1998) Screening for uveitis in juvenile rheumatoid arthritis. J Pediatr Ophthalmol Strabismus 34:41–43
1391 12. Sherry DD, Mellins ED, Wedgewood RJ (1991) Decreasing severity of chronic uveitis in children with pauciarticular arthritis. Am J Dis Child 145:1026–1028 13. Kotaniemi K, Kautianen H, Karma A et al (2001) Occurrence of uveitis in recently diagnosed juvenile chronic arthritis: a prospective study. Ophthalmol 108:2071–2075 14. Angeles-Han S, Yeh S (2012) Prevention and management of cataracts in children with juvenile idiopathic arthritis–associated uveitis. Curr Rheumatol 14:142–149 15. Kotaniemi K, Arkela-Kautiainen M, Haapasaari J, LeirisaloRepo M (2005) Uveitis in young adults with juvenile idiopathic arthritis: a clinical evaluation of 123 patients. Ann Rheum Dis 64:871–874 16. Paroli MP, Speranza S, Marino M et al (2003) Prognosis of juvenile rheumatoid arthritis-associated uveitis. Eur J Ophthalmol 13:616–621 17. Foster CS, Havrlikova K, Baltatzis S et al (2000) Secondary glaucoma in patients with juvenile rheumatoid arthritis-associated iridocyclitis. Acta Ophthalmol Scand 78:576–579 18. Rosenberg KD, Feuer WJ, Davis JL (2004) Ocular complications of pediatric uveitis. Ophthalmol 111:2299–2306 19. Kotaniemi K, Kotaniemi A, Savolainen A (2002) Uveitis as a marker of active arthritis in 372 patients with juvenile idiopathic seronegative oligoarthritis or polyarthritis. Clin Exp Rheumatol 20:109–112