Systemic sclerosis in childhood
Correspondence to: Dr Med. I. Foeldvari, Senior Consultant Pediatric Rheumatology Clinic, Allgemeines Krankenhaus Eilbek, Haus 6, Friedrichsberger Str. 60, D-22081 Hamburg, Germany. E-mail: sprechstunde{at}kinderrheumatologie.de
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Juvenile systemic sclerosis (jSSc) is a rare disease of childhood, and the amount of published data is limited. It appears that its clinical presentation differs from adult disease and the limited form affects only very few children. The organ involvement pattern differs also from the adult form. Prognosis seems to be better with a 5-yr survival of 95% of the jSSc patients.
The validation of the outcome measures for children with jSSc is currently in progress. Regarding effective treatment, there are no paediatric data and the paediatric rheumatologist needs to rely on the experiences in adult disease.
Juvenile systemic sclerosis (jSSc) is a rare disease during childhood. There are no exact epidemiological data regarding prevalence and incidence. It is suspected that 10% of all SSc patients develop the disease before the age of 18 yrs. According to current studies, the mean age of onset is 8.8 yrs [1, 2]. All available data on organ involvement and outcome are based on case reports and retrospective case collections, respectively. The recent large retrospective case collections and the German registry are summarized in the following.
Our group summarized the result of a multinational worldwide cross-sectional questionnaire-based survey of 135 jSSc patients from 34 paediatric rheumatology centres (response rate 14%) [1]. Of the 135 patients, 122 were Caucasian; 100 were female. The mean age at disease onset was 8.8 (± 3.3) yrs. The mean disease duration at the last follow-up was 5 (± 3.3) yrs. 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. Of the living patients, 90% were fully active in daily life. Eight of the 135 patients had died. These patients had a median age at onset of the disease of 10.5 yrs (range 6.7–15.8 yrs). The median disease duration until death was 2 yrs (range 1–8). The causes of death were heart failure (n = 5), renal failure (1), sepsis (1) and in one case the cause was not defined. Patients with fatal outcome had a higher rate of pulmonary (75 vs 49%), cardiovascular (100 vs 41%), renal (50 vs 10%) and central nervous system (38 vs 14%) involvement when compared with patients with a nonfatal outcome. The 1-, 2- and 4-yr survival rates were 99, 97 and 95%, respectively.
A recent study was performed during the classification project for jSSc and has already been published as an abstract [2]. A total of 153 jSSc patients from 55 centres were reported, who were in part identical with the ones reported in the aforementioned initial survey [1]. The ratio of female to male patients was 120:33, confirming the lower proportion of females in the paediatric compared with the adult SSc population. The time interval between onset of symptoms and definite diagnosis was 1.9 yrs (range, 0–12.3).The antibody profile of jSSc patients showed ANA positivity in 120 of 150 patients, and ENA positivity in 51 of the 120 ANA positive patients. Moreover, 36 of 106 tested patients were anti-Scl 70 positive. In this survey, 12 of 153 patients died. Mean duration from disease onset to death was 22.5 months (range, 4–120), similarly to the earlier survey [1]. Again, patients with fatal outcome showed a higher rate of pulmonary (75 vs 46%), cardiovascular (75 vs 15%) and renal (42 vs 5%) involvement as well as Raynaud's syndrome (83 vs 54%) when compared with the non-fatal group.
In a yet unpublished summary literature review (Table 1) summarizing 17 case reports of 51 jSSc patients with sufficient data regarding organ involvement, outcome and demographics, ethnic distribution and pattern of organ involvement was found to be similar when compared with the two aforementioned surveys: 39 of 51 patients were female, the mean age at diagnosis was 9.4 yrs and the mean follow-up period was 3.3 yrs.
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In terms of organ involvement, both surveys on jSSc [1, 2] revealed a similar pattern in jSSc compared with adult SSc patients (Table 1). For example, pulmonary involvement was found in 41–50%. However, there are no data allowing a differentiation between patients with interstitial lung disease and pulmonary hypertension. It can be assumed that interstitial lung disease might be the predominant underlying clinical problem as most patients showed diffuse skin involvement. In contrast, renal involvement was found to be
10% lower than in adult cohorts. The German Scleroderma Network (DNSS) with long-term information on 802 SSc patients provides data on only nine jSSc patients. It would be expected that 10% of the patients in adult cohort have an onset in childhood, but interestingly, this is the case in only 1%. Mean age at disease onset was 9.1 yrs (range, 2–17). The time span between diagnosis of jSSc and the onset of Raynaud's phenomenon was 2.1 yrs (range, 0–11). Mean follow-up of patients in the DNSS database was 20 yrs (ranging from 3 to 44 yrs). Four of the nine patients with disease onset at <18 yrs of age had diffuse involvement. The difference to the above survey of Foeldvari et al. [1] can be explained by the survival bias: patients with limited disease appear to have a better long-term prognosis compared with those with diffuse cutaneous involvement.
Preliminary classification criteria for jSSc have been developed by international paediatric and adult rheumatologists and dermatologists using the Delphi technique in order to shorten the time period from onset of first symptoms to definite diagnosis and unambiguously diagnose paediatric patients with SSc. [3]. The proposed criteria include one major criterion (sclerosis and/or skin induration specific for SSc) and eight minor criteria reflecting the relevant involved organ systems (e.g. pulmonary, cardiac, gastrointestinal, renal, vascular, musculoskeletal, neurological and serological involvement) [4]. Using this set of clinical symptoms, a paediatric patient is considered to suffer from jSSc if one major and two minor criteria are fulfilled. The validation of this proposed classification is currently ongoing, aiming at an earlier diagnosis of paediatric patients as compared with the current situation when applying preliminary criteria for SSc in adults.
In the adult ‘scleroderma world’, evaluation of outcome measures for each organ system has been initiated few years ago [5]. In contrast, the first efforts to validate outcome measures in paediatric SSc patients have just been started. In a prospective study, the Modified Rodnan Skin Score (MRSS) has been evaluated in a paediatric population showing good correlation with the Tanner stage and with gender [6]. However, MRSS has first to be adapted for pediatric patients until this test is ready for application in jSSc. Therefore, two clinical research teams have already examined the age-specific characteristics of capillary nailfold changes in children showing age-specific changes in both the capillary diameters and forms [7, 8].
Not only in terms of diagnostics but also regarding effective treatment there is no specific paediatric data available. Paediatric rheumatologists, therefore, need to use the existing adult experience. However, a multinational inception cohort for juvenile patients with recent onset of SSc is under preparation in order to obtain prospective standardized data on organ involvement, course of disease and effectiveness of the currently applied therapies in this specific population.
The author has received speaker's honorarium for participation at Actelion Winter School 2006.
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- Foeldvari I, Zhavania M, Birdi N, et al. (2000) Favourable outcome in 135 children with juvenile systemic sclerosis: results of a multi-national survey. Rheumatology 39:556–9.
[Abstract/Free Full Text] - Zulian F. (2005) Outcome in juvenile scleroderma syndromes. Ann Rheum Dis 64:Suppl. IIII, S34.
- Zulian F, Woo P, Athreya B, et al. (2005) Preliminary classification criteria for systemic sclerosis in children. Arthritis Rheum 52:Suppl., S533.
- Zulian F, Woo P, Athreya B, et al. (2005) Preliminary classification criteria for systemic sclerosis in children. Clin Exp Rheumatol 23:S43.[ISI][Medline]
- Merkel PA, Clements PJ, Reveille JD, Suarez-Almazor M, Valentini G, Furst DE. (2003) Current status of outcome measure development for clinical trials in systemic sclerosis. Report from OMERACT 6. J Rheumatol 30:1630–47.[ISI][Medline]
- Foeldvari I and Wierk A. (2006) Healthy children have a significantly increased skin score assessed with the modified Rodnan skin score. Rheumatology 45:76–8.
[Abstract/Free Full Text] - Herrick ML, Moore T, Hollis S, Jayson MIV. (2000) The influence of age on nailfold capillary dimension in childhood. J Rheumatol 27:797–800.[ISI][Medline]
- Dolezalova P, Young SP, Bacon PA, Southwood TR. (2003) Nailfold capillary microscopy in healthy children and in childhood rheumatic diseases: a prospective single blind observational study. Ann Rheum Dis 62:444–9.
[Abstract/Free Full Text]
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