Rheumatology 2000; 39: 556-559
© 2000 British Society for Rheumatology
Paediatric Rheumatology |
Favourable outcome in 135 children with juvenile systemic sclerosis: results of a multi-national survey
University Children's Hospital, Hamburg, Germany,
1 Medical University of Tbilisi, Georgia, Russia,
2 Children's Hospital of Eastern Ontario, Ottawa, Canada,
3 Hospital de Pediatria Pedro de Elizalde, Buenos Aires, Argentina,
4 Federal University of Rio de Janeiro, Rio de Janeiro, Brasil,
5 McMaster University, Hamilton, Ontario, Canada,
6 Department of Rheumatology, Lund University Hospital, Sweden,
7 Rheumatology Unit, University of Florence, Italy,
8 St Josef Stift, Sendenhorst,
9 University Children's Hospital, Würzburg,
10 Rheumakinderklinik, Garmisch-Partenkirchen, Germany,
11 Centre for Paediatric Rheumatology, University Gent, Belgium,
12 Wilhelmina Kinderziekenhuis, Utrecht, The Netherlands,
13 Children's Hospital, University of Helsinki, Finland,
14 Hôpital Necker Enfants Malades, Paris, France,
15 Paediatric Clinic, Institute of Rheumatology, Warszawa, Poland,
16 Hospital de Pediatria, Buenos Aires, Argentina,
17 Rheumatism Foundation Hospital, Heinola, Finland,
18 Paediatric Rheumatology Clinic, Department of Pediatrics, University of Ioannina, Greece and
19 Centro di Rheumatologia Pediatrica, University of Padova, Padova, Italy
Abstract
Objective. To increase the current knowledge of the outcome of juvenile systemic sclerosis (jSSc), which is currently limited.
Methods. In order to investigate the patient outcome and prognostic factors, starting October 1994, we distributed questionnaires to 324 paediatric rheumatology centres.
Results. Until 15 May 1998 responses from 46 centres were received, 34 of which returned completed questionnaires on a total of 135 patients. One hundred and twenty-two of the 135 patients were Caucasian, 100 were female. The mean age at disease onset was 8.8 yr (S.D. ± 3.3 yr). The mean disease duration at the last follow-up was 5 yr(S.D. ± 3.3 yr). At the last follow-up the disease was still active and required medication in 82 patients, 36 had inactive disease on medication, and 16 were in remission. Ninety per cent of the living patients were fully active in daily life at the last follow-up. Eight of the 135 patients had died. These patients had a median age at onset of the disease of 10.5 yr (range 6.7–15.8 yr). The median disease duration until death was 2 yr (range 1–8 yr). The causes of death were heart failure (five), renal failure (one), sepsis (one) and in one case the cause was not defined. The 1 yr survival rate was 99%, the 2 yr was 97% and the 4 yr was 95%.
Conclusions. At a mean follow-up of 5 yr, the current results show a favourable outcome in most patients with childhood onset jSSc and a significantly better survival than in the adult SSc patients.
KEY WORDS: Childhood, Outcome, Mortality, Morbidity, Survival.
Systemic sclerosis (SSc) is a rare disease in adults and children [1]. Patients with juvenile onset represent almost 10% of all patients with scleroderma [2]. Of all patients with SSc, 1.5% develop evidence of the disease before the age of 10 yr [3], and an additional 7.2% develop signs and symptoms between 10 and 19 yr of age [3]. Currently, information on survival and prognostic factors for survival in adult SSc patients is increasing [4–7], but is still lacking in regard to juvenile SSc (jSSc). To learn about jSSc, we distributed a survey to 324 paediatric rheumatology centres starting October 1994. In the following we present the final collected results as of 15 May 1998.
Methods
The questionnaire was addressed to paediatric rheumatologists in Europe, Canada, the USA and South America. The addressed centres were based on the mailing lists of the Paediatric Rheumatology Section of EULAR (kindly provided by A. M. Prieur), the mailing list of the Canadian Pediatric Rheumatology Group (kindly provided by P. N. Malleson) and the mailing list of the American Academy of Pediatric Rheumatology Section List (kindly provided by C. B. Lindsley). Mostly the mailing lists included the names of the heads of the paediatric rheumatology units, seldom was more than one person named from the same unit. The questionnaire was sent to 324 paediatric rheumatologists based on these lists.
Each questionnaire consisted of a covering letter and a multiple choice formula containing 34 questions, with space left for general comments. The questions focused on information about demography, presenting symptoms, diagnostic criteria, disease course, organ involvement, treatment and outcome during the follow-up period. The questions regarding organ involvement did not precisely define organ involvement, rather each participating physician was allowed to apply his or her own clinical judgement. All information was kept confidential.
Results
Forty-six centres (14%) responded. Thirty-four (26 European, three Canadian, two American, one Brazilian, two Argentinean) reported 137 patients. One hundred and thirty-five of the 137 patients fulfilled the American College of Rheumatology (ACR) preliminary criteria for the classification of SSc [8]. One hundred of the 135 patients were female, the mean age at disease onset was 8.8 ± 3.3 yr (range 1.5–15.8), and the mean disease duration at last follow-up was 5.0 ± 3.3 yr (range 0.3–21). Due to insufficient information, we could not evaluate the antibody profile of the patients.
In 82 patients the disease was still active on medication. Sixteen patients were in remission at the last follow-up. Ninety per cent of the living patients were fully active in daily life at the end of the follow-up.
Eight of the 135 patients had died, the median age at disease onset being 10.5 yr (range 6.7–15.8) and the median disease duration until fatal outcome 2.0 yr (range 1–8).
The antibody profile of these patients was determined and seven of the patients were antinuclear antibody (ANA) positive, in the eighth it was not determined. Anti-Sc170 was measured in four of the patients, in two of whom it was positive.
A comparison of the distribution of organ involvement in the surviving patients with those who died (Table 1
), revealed an increased proportion of pulmonary (P > 0.1), central nervous system (CNS) (0.1 > P > 0.05), cardiovascular (P < 0.01) and renal (P < 0.01) involvement in the group with fatal outcome. Seven of eight patients with fatal outcome died within the first 4 yr of the disease (Table 2). The 1 yr survival rate was 99%, the 2 yr was 97%, the 4 yr was 95%, and the 8 yr was 94%. Regarding therapy, a wide variety of medication was used, especially prednisone, hydroxychloroquine, D-penicillamine and methotrexate as non-steroidal anti-inflammatory drugs. Prednisone was used primarily as a first-line drug, but insufficient information was gained about the various schedules. The timing, dosages and type of application of the second-line drug were also quite varied, for example methotrexate was given in a dose ranging from 0.1 mg/kg up to 1 mg/kg once a week, applied orally, intramuscularly, or even intravenously. No definitive conclusion can be made based on the data available.
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Discussion
This study reports the final results of an international multi-centre survey of patients with jSSc. Although only 14% of the centres responded to the survey, we collected the largest database, until the present, regarding survival in jSSc, including data on 135 patients.
The relatively low response rate raises the issue of bias, but over the time lapse during data collection, initial results were summarized in poster presentations, first including 94 [9], then 105 [10], and later 120 [11] patients, and these partial results regarding survival and organ involvement remained stable over the entire collection period. This might suggest that despite the low response rate, the collected data could be representative.
Overall survival is a useful measure of outcome, especially in a rare disease with frequent fatal outcome [1]. We found a much better 5 yr survival rate of 95% than in the recently presented adult study including data from 1863 SSc patients in which a 5 yr survival rate of 78% was reported [12].
We compared the organ involvement in the group with fatal and non-fatal outcome and found a trend towards an increased number of patients with pulmonary and CNS involvement and a significant increase in cardiovascular and renal involvement in the group with fatal outcome. These results are similar to reports on adult patients [13, 14]. Simeon et al. [6] found functional vital capacity of less than 70% as a prognostic factor for increased mortality. The increased CNS involvement in our fatal group could reflect a systemic vasculitic involvement.
The distribution of the causes of death in our study (Table 2
), is similar to that in a recent Swedish presentation [15], in which cardiopulmonary involvement was also reported to be the most common cause of death. Renal crisis has been treatable since the availability of angiotensin-converting enzyme inhibitors (ACE). Only one patient in our survey died due to renal complication.
The amount of skin involvement, limited or diffuse, seems to be one of the major prognostic factors for survival [6, 16–18] in adult SSc. Unfortunately we cannot draw any conclusions regarding the amount of skin involvement in the patients in our survey. We know that all patients fulfilled the preliminary criteria for SSc, but do not know about the total skin involvement.
We did gain information about the disease activity in the patients with a non-fatal course. In 82% the disease was still judged to be active on medication and 16 patients were in remission while off medication, as judged by the physicians. Of the living patients, 90% were fully active in daily life at the end of the follow-up.
Our survey reveals that the survival rate of patients with jSSc is much better than that of adult patients. We conjecture whether this difference is a reflection of a slower disease progression or due to the significantly lower co-morbidity factors in the paediatric age group.
Acknowledgments
We thank all respondents who provided data.
Notes
Correspondence to: I. Foeldvari, University Children's Hospital, Martinistrasse 52, D-20246 Hamburg, Germany. 
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