To describe the long-term outcome of juvenile idiopathic arthritis (JIA).
To describe the long-term outcome of juvenile idiopathic arthritis (JIA).
All patients with JIA referred to a pediatric rheumatology center between 1978 and 1988 were identified and invited to undergo an assessment. Patients with JIA from a population-based cohort from East Berlin were included. The outcome assessment considered changes in body function and structure (e.g., mortality, joint abnormalities, disease activity), activities at the individual level (Health Assessment Questionnaire), and participation in society (e.g., mobility, educational and vocational background).
Of 260 eligible patients, 215 (83%) were evaluated. Subtypes of JIA at disease onset included oligoarthritis (40%), polyarthritis (14%), systemic arthritis (14%), psoriatic arthritis (1%), enthesitis-related arthritis (15%), and other arthritis (16%). Followup was conducted after a median of 16.5 years. No deaths occurred in this cohort. At followup, approximately half of the patients had active disease and/or changes in body structures to a variable extent. Approximately one-third of patients rated themselves as being functionally limited. Patients demonstrated good social integration: few mobility problems were reported, and the educational achievements of patients were higher and their rate of unemployment was lower compared with the age-matched population. No significant differences in outcome were found between the population-based and the referral-based cohorts.
Even though approximately half of the JIA patients had more or less distinctive changes in body function and/or structure after a disease duration of >15 years, fewer than 10% were severely disabled or handicapped. Because JIA often persists into adulthood, long-term followup and care are necessary.
Outcome assessment in rheumatic disorders is receiving more attention, not only in adults but also in the pediatric population. This is reflected in the increasing number of studies conducted in recent years (1–11) regarding the long-term prognosis of children with chronic arthritides. These studies have shown that chronic arthritis in children has a multidimensional impact on their lives. This impact can be perceived as a spectrum encompassing on one end “hard” disease outcomes such as mortality or organ failure, and on the other end “soft” outcomes such as quality of life or psychological status (12).
There are several ways to describe the various outcome aspects of juvenile idiopathic arthritis (JIA). In the current study, we used the revised International Classification of Impairments, Disabilities and Handicaps (13). According to the dimensions defined (body functions and structure, activities, and participation), we now report outcomes of adolescents and adults with JIA.
In planning our long-term followup study, a specific feature of the health care system in the former German Democratic Republic was an important factor. Because of governmental instructions that all children be regularly examined by pediatricians and that those with suspected rheumatic diseases be referred to specific centers, from the 1960s until 1989, every child with arthritis attended one of the few pediatric rheumatic disease centers. In the Berlin region, the referral center was the 2nd Children's Hospital at Berlin-Buch, where children from East Berlin as well as those from regions other than Berlin received care. As stated by Kiessling et al (14), it can be assumed that for the years studied, “virtually all children” from East Berlin with a chronic joint disease were treated there. This assumption was justified by the high number of referred patients with suspected JIA, the high proportion of cases of oligoarthritis, as well as concordance of the expected and observed numbers of JIA cases in the regions of Berlin closest to or farthest from the 2nd Children's Hospital. Therefore, we were able to recruit a patient cohort that consisted of both a referral-based group and a population-based group that attended this hospital.
The patients included in this followup study were recruited from a previously described cohort of patients with juvenile chronic arthritis and juvenile spondylarthropathy (14, 15). For the current study, we extended the time period during which patients were referred in order to recruit a larger cohort. Thus, patients from East Berlin who had disease onset between 1978 and 1988 (n = 93) were included in the population-based cohort. The referral-based cohort comprised all patients with chronic arthritis who were referred to the 2nd Children's Hospital at Berlin-Buch between 1978 and 1988 (n = 167). These patients were identified by reviewing the standardized medical records of all patients treated at this hospital. Only patients who fulfilled the International League of Associations for Rheumatology (ILAR) criteria for JIA (16) at disease onset and who were at least 15 years of age in December 1999 were eligible. The entire cohort comprised 260 patients with JIA.
During the years 1998 and 1999 and with the help of the residents' registration offices, we attempted to locate all patients. First, we mailed all 260 eligible patients an invitation to receive a reassessment at the 2nd Children's Hospital. If no reply was received within 2 months, we attempted telephone contact. A second letter was sent to those patients who could not be reached by telephone. In the end, 215 patients were evaluated (Figure 1). Of these, 133 had been previously assessed in the retrospective 7-year followup study (15).
Each patient's type of disease at onset was determined retrospectively according to the ILAR criteria. All diagnoses were determined independently by 2 pediatric rheumatologists (KM and TB). The followup diagnosis of ankylosing spondylitis (AS) was assigned to patients who fulfilled the modified New York criteria (17). For this purpose, available anteroposterior radiographs of the pelvis or magnetic resonance (MR) images were evaluated by a radiologist (MB), who graded features of the sacroiliac joints on the basis of the modified New York criteria for AS. MR images were evaluated according to the criteria described by Bollow et al (18). The diagnosis of sacroiliitis was established if conventional radiographs showed grade 2 or higher or if MR images revealed a chronicity index score of ≥2.
For this study, a patient was considered to be in complete remission if at followup he or she had no inflammatory spinal pain (defined according to European Spondylarthropathy Study Group criteria ), no active uveitis, had been receiving no drugs for 2 or more months, and fulfilled at least 5 of the American College of Rheumatology criteria for clinical remission in rheumatoid arthritis (20). These remission criteria included the following: morning stiffness not exceeding 15 minutes, no fatigue, no joint pain, no joint tenderness, no swelling in joints or tendon sheaths, and erythrocyte sedimentation rate (ESR) <20 mm/hour. Patients were classified as having partial remission at followup if they had no evidence of active disease but still required some form of drug therapy.
The assessment of patients was based on 2 self-administered paper-and-pencil questionnaires, a standardized interview, and a clinical evaluation (both performed by KM). Laboratory investigations included a complete blood cell count and determination of the ESR (mm/hour), immunoglobulin levels, antinuclear antibody titers (tested by indirect immunofluorescence using HEp-2 cells and considered positive when titers were ≥1:160 according to the standard of the laboratory), presence of rheumatoid factor (tested by nephelometry and considered positive when titers were >10 units/ml), and HLA–B27 (tested by polymerase chain reaction and available for 90% of patients). In addition, all available medical records were reviewed to ensure accuracy of the patients' interview information.
Because we had access to medical records from 3 rheumatology units, we were able to review the data of one-third of the patients who were still receiving care for rheumatologic disorders. Furthermore, almost one-third of the patients attended the reassessment accompanied by their parents, bringing copies of all of their medical records. Using this information and medical records from the 2nd Children's Hospital, we checked the interview data and found no relevant differences between information provided by the patients and that given in the records. The survey was tested in advance in a sample of young adults with arthritis who were attending the adult rheumatology department of the hospital in Berlin-Buch and was revised accordingly. The study was approved by the local ethics committee, and all participants gave their informed consent.
The first questionnaire, containing sociodemographic questions, the Health Assessment Questionnaire (HAQ) (21), and questions about the patient's educational and vocational background, was mailed to all patients with instructions to complete it 1 day before the clinical examination. The questionnaire also contained 11-point numeric rating scales (NRS-11), which enabled patients to rate their pain, functional limitation, disease activity, and overall well-being. Patients were requested to select a number on the scale (0 = best, 10 = worst) that best reflected their status within 7 days prior to the assessment.
The assessment at the hospital included a clinical examination (including a 42-joint count) and the physician's rating of the patient's functional status according to Steinbrocker criteria (22). An interview was conducted regarding the course of disease, treatments received, and the number of surgeries the patient underwent after leaving the 2nd Children's Hospital. The patient's current health care status was also recorded. In addition, patients were asked to complete a second questionnaire that contained mainly standardized instruments such as the German version of the Rheumatoid Arthritis Quality of Life Questionnaire (23) and the German 15-item version of the Center for Epidemiologic Studies Depression Scale (24). Furthermore, participants assessed the current burden of illness in terms of their physical, emotional, financial, and family situation on a 4-point Likert scale ranging from “not at all” to “very much.” All patients participated in the complete assessment, except for 2 who refused blood tests and 16 others who were unable to come to the hospital for various reasons. The latter group of patients completed the questionnaires at home and were interviewed by phone.
Data were analyzed using the SPSS Statistical Package for the Social Sciences (25). The Mann-Whitney test and the chi-square test for categorical data were used for statistical comparisons when appropriate. The 5% significance level was used for all analyses.
Relationships between disease parameters were studied using Spearman's rank correlation. In addition, analysis of variance (ANOVA) was used to explore the effect of various parameters (e.g., arthritis subgroup, sex, disease activity, and disease duration) on patients' followup status.
Data from 215 patients were considered in this analysis. These patients were first seen at the hospital after a median disease duration of 4 months (interquartile range [IQR] 0–127) and were treated there for a median of 16 years (IQR 3–24). The median followup period was 16.5 years (range 10–30) after disease onset or 8 years (range 0–19) after leaving the 2nd Children's Hospital.
Patient characteristics according to the various ILAR subgroups are shown in Table 1. Patients in the population-based cohort did not differ significantly from those in the referral-based cohort regarding sex, age at disease onset, and followup. There was also no significant difference between cohorts in terms of subgroup distribution. However, relatively more patients with systemic arthritis were in the referral-based cohort.
|Cohort||n||% female||Median age at onset (range)||Median age at followup (range)|
|Systemic arthritis||30||47||4 (0–15)||20 (14–31)|
|Oligoarthritis||85||60||4 (1–14)||21 (14–34)|
|RF+||3||100||12 (12–13)||29 (24–32)|
|RF−||27||85||7 (1–13)||22 (14–36)|
|Psoriatic arthritis||3||33||12 (12–15)||30 (24–31)|
|Enthesitis-related arthritis||33||24||11 (4–15)||25 (17–35)|
|Other arthritis||34||49||8 (1–15)||25 (15–34)|
|Total||215||54||6 (0–15)||23 (14–36)|
|Systemic arthritis||5||60||4 (2–7)||20 (17–24)|
|Oligoarthritis||29||59||5 (1–13)||21 (14–32)|
|RF−||9||78||7 (1–12)||22 (17–28)|
|Enthesitis-related arthritis||12||17||9 (5–14)||25 (17–35)|
|Other arthritis||17||41||8 (2–14)||25 (16–33)|
|Total||74||50||7 (1–15)||22 (14–35)|
Among patients with oligoarticular-onset JIA, approximately one-third (n = 26) had polyarticular extension of disease. Furthermore, 7% of patients in this group had psoriatic arthritis, 2% had definite AS, 6% had possible AS (no radiographs or MR images were available), and 1% had arthritis associated with inflammatory bowel disease at followup. Among patients with enthesitis-related arthritis (ERA), of whom 76% reported having had current (within the 2 months prior to assessment) inflammatory back pain, 39% had definite AS and 36% had possible AS at followup.
Forty-two patients were lost to followup, including 22 with oligoarthritis, 9 with ERA, 1 with systemic arthritis, and 6 with polyarthritis. No patient with psoriatic arthritis was lost to followup. The median age of the patients who were not reassessed was 24 years (range 15–33), and 50% of them were men. More nonparticipants than participants left the 2nd Children's Hospital in complete remission (52% versus 36%). Based on outcome data (including Steinbrocker functional class) from the 7-year followup study, which was available for 43% of the nonparticipants (8 with oligoarthritis, 5 with polyarthritis, 2 with ERA, and 3 with other arthritis), nonparticipants had better functional status compared with participants. Sixty-one percent of nonparticipants were regarded as being in functional class I, compared with 49% of participants; 39% of each group was in functional class II; 0% and 10%, respectively, were in functional class III; and 0% and 2%, respectively, were in functional class IV. Thus, it is likely that mainly patients with milder disease were lost to followup.
Mortality. There was no fatal disease outcome among the patients. Because of our access to the residents' registration offices, we were also able to exclude death among those patients who were not evaluated. Therefore, a mortality rate of <1.5% can be assumed (95% confidence interval [95% CI] 0, 1.4).
Amyloidosis. Three patients (1.4%) (95% CI 0.5, 4.0) developed amyloidosis; 1 of these patients had systemic arthritis and the other 2 had extended oligoarthritis.
Malignancy. One patient with ERA who had never received immunosuppressive therapy was treated for a thyroid carcinoma 6 years prior to the examination.
Organ failure. Eye. Thirty-one patients experienced uveitis after a median disease duration of 4 years (range, 13 years before to 18 years after arthritis onset); 2 of these patients lost their eyesight due to uveitis (Table 2). Uveitis was more often seen in the ERA group (24%) than in the oligoarthritis group (16%), but no significant difference in the frequency of uveitis among the various subgroups was observed. Fifteen (48%) of the 31 affected patients (7% of the whole cohort) reported having developed sequelae due to uveitis, resulting in reduced eyesight in 80% of the 15 patients. Eight of these 15 patients had to undergo at least 1 eye operation; for 6 of these patients, the surgery was for cataract removal. At followup, 4 patients were still receiving local treatment of uveitis; 2 of them had had remissions of arthritis for a median of 17 years.
|JIA subgroup||All patients (n = 215)|
|Oligoarthritis (n = 85)||Polyarthritis RF− (n = 27)||ERA (n = 33)||Other (n = 34)|
|No. (%) with uveitis||14 (16)||3 (11)||8 (24)||6 (18)||31 (14)|
|No. ANA positive|
|No. HLA–B27 positive||3||1||8||3||15|
|No. of years from disease onset to diagnosis of uveitis, median (IQR)||4 (0–6.25)||3 (1–10)||5 (0.25–10.25)||8 (1.5–13)||4 (0–10)|
|No. (%) with sequelae due to uveitis||8 (9)||1 (4)||3 (9)||3 (9)||15 (7)|
Heart. Heart involvement within the scope of the rheumatic disease was observed in 5% of all patients: 8 had a history of pericarditis, and 4 had a history of myocarditis. Two of these patients had amyloidosis and extended oligoarthritis, and the others had systemic arthritis. Only 1 patient with systemic arthritis reported having had perimyocarditis within the previous 12 months as part of a disease exacerbation, and the others reported no current heart problems. Only 3 of the patients with cardiac involvement were receiving β-blocking substances, calcium antagonists, angiotensin-converting enzyme inhibitors, and/or diuretics at followup; these were the 2 patients with amyloidosis and the patient who had recently experienced perimyocarditis.
Kidney. One of the 3 patients with amyloidosis had developed renal insufficiency that was still being compensated. None of the other patients in the cohort, all of whom were treated with nonsteroidal antiinflammatory drugs, often for years, had experienced severe renal problems.
Growth disturbances. Three patients older than age 19 years achieved a final height that was below the third percentile: 2 women (1 with systemic arthritis and 1 with seropositive polyarthritis) and 1 man with systemic arthritis. Among the whole group of female patients, the median height was 166 cm (range 148–186 cm), which is lower than the median height (168 cm) among women in the general population (26). Among male patients, the median height was 179 cm (range 143–204 cm), compared with the average height (180 cm) among men in the general population. The lowest median heights were observed in the group with systemic arthritis: 164 cm for women and 173 cm for men. However, no significant differences between subgroups were observed.
Local growth disturbances were much more common and were notable in about 1 of every 4 patients. Limb length discrepancies (average 1 cm) were observed most frequently, occurring in 52 patients (33% of whom used shoe lifts). More than half of these patients (56%) had undergone a knee synovectomy early in the course of their disease; however, a significant correlation between synovectomy and limb length discrepancy was not found. Micrognathia was the next most common growth abnormality, seen in 9.5% of all patients, none of whom had received a mandibular correction. Twenty-two percent of patients with polyarticular JIA (rheumatoid factor–negative), 13% with systemic JIA, 8% with oligoarticular JIA, and 6% with other JIA were affected, and all but 2 of them had experienced a polyarticular disease course. Growth abnormalities of toes and feet were seen in 8.5% and 7% of patients, respectively.
Joint abnormalities. The number of patients having swollen or tender joints and/or joints with limited range of motion (ROM) (joint motion outside the normal range according to the neutral-0 method) (27) is shown in Table 3. Joint operations had been performed on 45% of patients during the course of their disease. These surgeries were mainly synovectomies, which were performed on 72 patients an average of 3 years after disease onset. Only 5 patients (2%) had received an endoprosthesis after a mean ± SD disease duration of 13.5 ± 6.1 years. In all patients these were hip replacements; however, 1 patient had had 2 hip prostheses implanted and another patient had 2 hip prostheses and 1 knee prosthesis.
|Patient Group||Swollen/tender joints||Joints with limited ROM|
|Systemic arthritis||8 (28)||3 (10)||6 (21)||13 (45)|
|Oligoarthritis||17 (22)||9 (12)||22 (28)||9 (12)|
|RF+||1 (33)||2 (67)||0||3 (100)|
|RF−||8 (31)||7 (27)||5 (19)||16 (62)|
|Psoriatic arthritis||1 (33)||1 (33)||1 (33)||1 (33)|
|Enthesitis-related arthritis||8 (30)||2 (7)||9 (33)||9 (33)|
|Other arthritis||9 (27)||5 (15)||12 (36)||10 (30)|
|Complete remission||3 (4)*||0||18 (22)||6 (7)|
|All patients with active disease||43 (41)||26 (25)||34 (32)||48 (46)|
|All patients||52 (26)||29 (15)||55 (28)||61 (31)|
Disease activity at followup. Disease activity at followup was assessed by the physician according to remission criteria (Table 4), as well as by the patient (Table 5) and the physician on an NRS-11. The correlation between patients' and physicians' assessments of disease activity ranged from 0.69 for other JIA to 0.84 for ERA (0.75 for the whole group). In 46% of assessments of disease activity, patients and physicians were in agreement about the number chosen on the NRS-11, while in 31% the physician rated the disease activity higher (median 1 point) than did the patient, and in 23% the patient rated disease activity higher (median 2 points) than did the physician.
|Whole cohort (n = 215)||Population-based cohort (n = 74)|
|Systemic arthritis||2 (7)||14 (47)||1 (20)||3 (60)|
|Oligoarthritis||4 (5)||46 (54)||3 (10)||14 (48)|
|RF−||3 (11)||8 (30)||3 (33)||2 (22)|
|Psoriatic arthritis||0||1 (33)||0||0|
|Enthesitis-related arthritis||1 (3)||6 (18)||0||2 (17)|
|Other arthritis||0||12 (35)||0||6 (35)|
|Total||10 (5)||87 (40)||7 (9)||27 (36)|
|Patient group||Disease activity||Pain||Morning stiffness||Antirheumatic treatment|
|Systemic arthritis||13 (45)||15 (52)||9 (30)||6 (20)||12 (40)|
|Oligoarthritis||41 (48)||44 (52)||24 (28)||15 (18)||18 (21)|
|RF+||3 (100)||3 (100)||2 (67)||2 (67)||2 (67)|
|RF−||19 (70)||17 (63)||14 (52)||4 (15)||7 (26)|
|Psoriatic arthritis||2 (67)||2 (67)||0||1 (33)||1 (33)|
|ERA||18 (56)||20 (63)||17 (52)||9 (27)||9 (27)|
|Other||17 (50)||15 (44)||14 (41)||8 (24)||6 (18)|
|Total||113 (53)||116 (55)||80 (37)||45 (21)||55 (26)|
According to patient-supplied data, 47% of patients rated their disease as being inactive (NRS score = 0). Most participants who described their disease as still being active rated disease activity as low, with a median NRS score of 3 (IQR 1–5). Patients' data for disease activity were correlated with their data for pain (r = 0.9, P < 0.01) and overall well-being (r = 0.71, P < 0.01), number of swollen/tender joints (r = 0.62, P < 0.01), and number of joints with limited ROM (r = 0.49, P < 0.01). In contrast, disease duration was not correlated with disease activity at followup (r = −0.058, P = 0.4). In addition, no significant correlation between sex or disease subgroup and patients' data for disease activity was found by ANOVA.
The remission rate was highest (54%) in the subgroup of patients with oligoarthritis, with remission rates of 73% among those with persistent oligoarthritis and 12% among those with extended oligoarthritis. Significant differences were observed between the remission rates of patients with oligoarthritis and those with seronegative polyarthritis (P = 0.04), those with oligoarthritis and those with ERA (P = 0.00), and patients with systemic arthritis and those with ERA (P = 0.01). When remission rates for patients in the population-based cohort were compared with those in the referral-based cohort, no significant differences were found between the global rates, which differed by only 4% (95% CI −9, 17), or between remission rates for the respective subgroups. However, the small number of patients in the various subgroups has to be kept in mind.
HAQ score. The HAQ was used to measure functional disability, which refers to “activities at the individual level.” A mean score of 0.22 (median 0, range 0–2.5) was obtained for all patients. Sixty-one percent of patients reported no disability (HAQ score = 0), while 12% had a score ≥0.75, and 6.5% had a score ≥1.0. The HAQ scores correlated with Steinbrocker functional classes (r = 0.73); correlations with other disease variables are shown in Table 6. The correlation of disease duration (10–14 years, 15–19 years, and 20–30 years), disease activity (0, 1–3, 4–6, 7–10 on NRS-11), ILAR subgroups, and sex with the HAQ score was analyzed by ANOVA and revealed a significant correlation only with disease activity (P = 0.00) (Figure 2). However, there was a tendency toward worse functioning with longer disease duration (P = 0.065), as illustrated by an increasing adjusted mean HAQ score (from 0.17 for patients with disease duration of 10–14 years to 0.31 for those with disease duration of 20–30 years). When comparing HAQ scores of the different ILAR subgroups, only a tendency (P = 0.076) for a worse functional status in patients with polyarthritis was found, with adjusted mean HAQ scores of 0.54 for seropositive polyarthritis, 0.39 for seronegative polyarthritis, 0.27 for systemic arthritis, 0.18 for oligoarthritis, and 0.16 for ERA.
|Variable||Median (interquartile range)||Correlation with HAQ score|
|Disease activity score, NRS 0–10||1 (0–3)||0.70†|
|Pain score, NRS 0–10||1 (0–3)||0.69†|
|RA-QoL questionnaire score, scale 0–30||1 (0–5)||0.69†|
|No. swollen/tender joints||0 (0–2)||0.64†|
|Overall well-being score, NRS 0–10||1 (0–3)||0.63†|
|No. joints with limited ROM||2 (0–6)||0.59†|
|CES-D score, scale 0–45||4 (2–7)||0.33†|
|Erythrocyte sedimentation rate, mm/hour||10 (3–20)||0.20†|
|Age at onset, years||6 (3–10)||0.09|
|Disease duration, years||16.5 (13–20)||0.08|
Steinbrocker functional class. According to physicians' assessment of patients' capacity to perform activities of daily living, based on Steinbrocker functional classes, 10% of all patients were considered to be Steinbrocker functional class III (21 patients) or IV (1 patient). Fifty-five percent of the patients had no limitations, and 35% had mild to moderate limitations, corresponding to Steinbrocker functional classes I and II, respectively. Among patients who were evaluated both after 7 years and after 17 years, Steinbrocker functional class distribution was as follows: class I, 49% and 55%, respectively; class II, 39% and 33%, respectively; class III, 10% and 11%, respectively; and class IV, 2% and 1%, respectively. Approximately one-third of patients (34 of 98) had a change in Steinbrocker class over time. Twenty-one of them had a change to a better class, and 13 experienced a change to a worse class. All patients except 1 changed by only 1 class.
Need for help and assisting devices. According to the HAQ, 21 patients (10%) needed assistance with activities of daily living such as “other activities” (n = 15), “reach” (n = 7), and/or “dressing” (n = 5). Nineteen patients (9%) required aids (e.g., for dressing [n = 8], hygiene [n = 8], and/or grip [n = 6]). In total, 13% of all participants (37% of patients with polyarthritis) reported the need for assistance and/or aids in order to engage in their daily routines.
Mobility. Although one-third of the patients reported having difficulty walking long distances (according to the RA-QoL), only 1 patient had severe mobility problems at followup. This patient was a young woman who constantly depended on a wheelchair. Two other patients also required use of a wheelchair, but only occasionally, and another 3 occasionally needed to use crutches.
Educational level and employment status. The 20–35-year-old patients in the cohort achieved an educational level comparable to or even higher than that of age-matched individuals in the corresponding general population (Table 7). Five percent of the participants had achieved their secondary school qualification at a school for physically disabled children. Patients' vocational background as well as their current employment status are shown in Table 7. At followup, more than half of the 20–35-year-old patients were employed (mainly as white-collar workers), about one-fourth were still completing their vocational training, and 5% were unable to work for health-related reasons and received a disability pension.
|Variable||Population (n = 1,219,200)||Study cohort (n = 151)|
|Not completed or without school qualification||6||6 (3–11)|
|Lowest school level||13||4 (2–9)|
|Intermediate school level||48||50 (42–58)|
|High school graduate||33||39 (32–48)|
|Not stated||6||1 (0–4)|
|Not completed, unskilled||27||26 (20–34)|
|Semiskilled, vocational school||56||59 (51–66)|
|College or university degree||11||15 (10–21)|
|Other status or vocational training||16||35 (28–43)|
|Work disability||3||5 (2–9)|
|Employed part-time||12||5 (3–10)|
|Employed full-time||57||50 (42–58)|
Family. Twenty-eight percent of the 20–35-year-old patients lived alone, 52% lived with a partner, and 18% lived with their parents. One-fourth of the patients had children; most (76%) had 1 child, 21% had 2 children, and 1 patient (3%) had 3 children. Although all but 2 patients were able to live independently, one-fourth reported regularly receiving support from their relatives in their daily routines.
Global burden of illness. Overall, 59% of all patients considered themselves to be physically burdened and 37% felt emotionally burdened by their illness at followup. Conversely, only 17% thought that their disease was currently putting a burden on their family lives, and 14% thought that their disease was a burden on their friends. Only a few more (24%) reported that the disease created a financial burden, but 44% claimed to be somehow burdened by the illness in terms of his or her professional goals or at the workplace. Patients with active disease considered the burden to be greater than did those with inactive disease, although this perception of greater burden was less pronounced in the domains of family and friendship (22% of these patients felt burdened in each case) than in the professional (62%), physical (87%), and emotional (54%) domains.
Comparison between the population-based and referral-based cohorts. Outcome data from the population-based cohort were compared with those from the referral-based cohort, and no significant differences were found with regard to disease duration, frequency of uveitis, remission rates, patient-reported disease activity and pain, ESR, number of tender/swollen joints, number of joints with limited ROM, functional limitation (HAQ score), quality of life (RA-QoL score), educational level, and employment status (data not shown).
In this 17-year followup study, the majority of patients with JIA had a favorable outcome, even though changes in body function and structure were observed in more than half of the adolescents and adults at followup. However, the observed changes were often very mild and did not always result in functional limitation or a perceived burden of illness. Key outcome features such as mortality or amyloidosis turned out to be not as relevant as they were years ago (29, 30), with a mortality rate of 0% (or at least <1.5%) and an amyloidosis rate of 1.4%. The same applies to severe extraarticular organ damage, which was experienced by 1.4% of patients, 2 of whom lost their eyesight because of uveitis.
In this JIA cohort, ocular involvement was the most common extraarticular manifestation and was observed in 14% of patients, which is comparable with findings of recent studies on uveitis in juvenile arthritis (31, 32). Uveitis was most often experienced by patients with ERA, predominantly as symptomatic uveitis, and no patient in the group with psoriatic arthritis had uveitis. This may be attributable to the small number of patients fulfilling the ILAR inclusion criteria for psoriatic arthritis. Otherwise, uveitis was seen in 4 of the 17 patients who had both arthritis and psoriasis. Half of the patients with uveitis reported having developed sequelae due to uveitis, as manifested by reduced eyesight in 12 patients. The extent of vision loss could not be ascertained, however, because an ophthalmologic examination was not part of the followup assessment.
Other changes in body function and structure included tender/swollen joints (41% of patients), restrictions in joint motion (54%), and local growth disturbances (26%). The prevalence of the latter appeared to be relatively high, with limb length discrepancies representing most of the growth disturbances. The clinical importance of this finding is questionable, however, because the majority of patients had leg length differences of 1 cm or less. Furthermore, because even in the general population, the frequency of leg length inequalities of 1 cm or more is reported to be 23% (33), this finding as a JIA-related outcome parameter must be checked by including a control group.
The relatively high number of joint operations (performed on 45% of all patients) does not reflect joint damage but rather the formerly used therapeutic strategy of “early” synovectomy in order to prevent disease progression. The data are not appropriate for assessing the effect of this procedure on outcome, but they give the impression that synovectomies at least did not prevent the above-mentioned changes, such as residual restrictions in joint motion or limb length discrepancies.
Approximately half of the patients had active disease at followup, usually at a low level. This proportion is in the range of 37–66%, which was reported in previous long-term outcome studies (3, 9). We found that remission rates in the population-based and referral-based cohorts were comparable, leading to the assumption that the remission rates of the whole cohort are representative. Patients with oligoarticular-onset JIA were most often in remission; the remission rate was only 54%, however, probably because of the heterogeneity of this group. Almost half of patients with oligoarthritis had developed polyarticular arthritis or a form of spondylarthropathy (e.g., AS) over the course of their disease, for which remission rates were 12% and 0%, respectively. A comparable rate of subtype change was described by Guillaume et al (10), who reported that among patients with oligoarticular-onset JIA, the probability of a polyarticular course was 50%, and that the remission rate was only 36%. In addition, we found the very low remission rate of 18% for patients with ERA. The high prevalence of current inflammatory back pain, an exclusion criterion for remission, was responsible for this low rate. At followup, 39% of the patients with ERA had definite AS, and 36% had possible AS. These figures are similar to those reported by other investigators (34, 35).
In the present study, 6.5% of patients had an HAQ score of 1.0 or higher, and 10% were severely disabled according to Steinbrocker functional class status; these figures are in accordance with those of other recent studies of JIA outcome (5, 9). Changes in body function and structure (e.g., disease activity and joint abnormalities) correlated with functional limitation at followup. Current disease activity had the strongest influence on functional status, and disease duration was not significantly correlated with the HAQ score. This finding was somewhat unexpected, because other long-term studies have shown that the fraction of disabled patients clearly increased in association with longer time-span to followup (9, 36, 37). The fact that we found only a tendency for a worsening of functional status with increasing disease duration could be attributable to patients' adaptations to their limitations. The patients could have changed their perception of their abilities gradually, so that the HAQ score does not correctly reflect functional loss over time, a fact also stated by Wolfe (38).
Functional status as rated by the physicians also did not worsen over time. This is shown by comparing the Steinbrocker functional classes of patients assessed in both the 7-year and 17-year-followup studies. Therefore, the data suggest that current disease activity, pain, and psychological factors are more relevant than disease duration in terms of patients' functional status at followup.
Because a successful transition from school to work plays a key role in the social integration of adolescents with arthritis, a patient's employment status might best reflect the social consequences of JIA. In this cohort, more than half of the 20–35-year-old patients were employed at followup, but one-fourth of the patients in this age group were still completing vocational training, possibly deferring their transition into the work force. The unemployment rate observed among patients in our study was lower than that in the corresponding age-matched population. This finding contradicts those of other investigators (3, 6), who reported significantly increased unemployment rates in adults with a history of JIA compared with controls, despite similar or even better attainments in formal education. The latter finding was also observed in our study.
Despite the good physical functioning and social integration of the patients in general, many patients, especially those with active disease, felt burdened by their illness and were in need of care. Therefore, the question arises whether more intensive therapy in adulthood might have improved outcome, considering the number of patients receiving NSAIDs (21%) or DMARDs (26%) at followup.
As with any study, our results must be interpreted in light of certain limitations. First, we relied on data from the 2nd Children's Hospital, where only recognized and referred patients were treated. Thus, the possibility that some undetected cases were missed cannot be ruled out. Second, no control group was included, which limits the capacity to make comparisons. Third, 16% of the patients (mainly those with oligoarthritis) were lost to followup, which might have biased the results. Finally, we used one standardized measurement for all patients, which could not consider the specifics of the various JIA subgroups.
In summary, although very severe disease outcomes in JIA are more rare than they were decades ago, JIA-related morbidity in adulthood is still evident. When interpreting these results, it must be kept in mind that the outcome data relate to patients who became ill and were treated 10–30 years ago. Therefore, they received therapy that is somewhat different from that currently provided. Further studies will show if the long-term outcome in JIA patients treated today is, as expected, better than that of patients in this cohort.
We are particularly grateful to the patients who participated in this study. We also thank all physicians and nurses who provided data for their patients. We are extremely grateful to Eva Döring, MD, without whom this study could not have taken place.