Challenges in the diagnosis and treatment of juvenile systemic sclerosis

Abstract

During the past 10 years, descriptions of large registries of children with juvenile systemic sclerosis (jSSc) have improved our knowledge of this disease. jSSc differs from the adult disease in presentation as well as disease course. Two courses of disease have been described: a rapidly progressive and fatal illness with cardiac involvement; and, more commonly, a chronic course with less overall mortality. Subclinical disease, especially cardiac and pulmonary disease, should be specifically sought and appropriately monitored, particularly in the first years of disease. Use of screening pulmonary function tests and high-resolution CT increases the chance of detecting interstitial lung disease. Close attention needs to be paid to cardiac health, with improved understanding of the specific causes of death to aid in the development of preventive measures. Therapies that best balance risks and benefits are likely to differ between children and adults. Given the relative rarity of jSSc, pediatric trials will require multinational collaborative efforts.

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Figure 1: Severe digital insufficiency ulcers with differing degrees of healing from severe Raynaud phenomenon in a child with systemic scleroderma.
Figure 2

References

  1. 1

    Zulian, F. et al. Juvenile localized scleroderma: clinical and epidemiological features in 750 children. An international study. Rheumatology (Oxford) 45, 614–620 (2006).

    CAS  Article  Google Scholar 

  2. 2

    Foeldvari, I. et al. Favourable outcome in 135 children with systemic sclerosis: results of a multi-national survey. Rheumatology (Oxford) 39, 556–559 (2000).

    CAS  Article  Google Scholar 

  3. 3

    Martini, G. et al. Systemic sclerosis in childhood: clinical and immunological features of 153 patients in an international database. Arthritis Rheum. 54, 3971–3978 (2006).

    CAS  Article  Google Scholar 

  4. 4

    Scalapino, K. et al. Childhood onset systemic sclerosis: classification, clinical and serologic features, and survival in comparison with adult onset disease. J. Rheumatol. 33, 1004–1013 (2006).

    PubMed  Google Scholar 

  5. 5

    Zulian, F. et al. The Pediatric Rheumatology European Society/American College of Rheumatology/European League against Rheumatism provisional classification criteria for juvenile systemic sclerosis. Arthritis Rheum. 57, 203–212 (2007).

    Article  Google Scholar 

  6. 6

    Hunzelmann, N. et al. The registry of the German Network for Systemic Scleroderma: frequency of disease subsets and patterns of organ involvement. Rheumatology (Oxford) 47, 1185–1192 (2008).

    CAS  Article  Google Scholar 

  7. 7

    Foeldvari, I. & Wierk, A. Healthy children have a significantly increased skin score assessed with the modified Rodnan skin score. Rheumatology (Oxford) 45, 76–78 (2006).

    CAS  Article  Google Scholar 

  8. 8

    Leroy, E. C. et al. Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J. Rheumatol. 15, 202–205 (1988).

    CAS  PubMed  Google Scholar 

  9. 9

    Nigrovic, P. A., Fuhlbrigge, R. C. & Sundel, R. P. Raynaud's phenomenon in children: a retrospective review of 123 patients. Pediatrics 111, 715–721 (2003).

    Article  Google Scholar 

  10. 10

    Dolezalova, P., Young, S. P., Bacon, P. A. & Southwood, T. R. Nailfold capillary microscopy in healthy children and in childhood rheumatic disease: a prospective single blind observational study. Ann. Rheum. Dis. 62, 444–449 (2003).

    CAS  Article  Google Scholar 

  11. 11

    Silver, R. M., Miller, K. S., Kinsella, M. B., Smith, E. A. & Schabel, S. I. Evaluation and management of scleroderma lung disease using bronchoalveolar lavage. Am. J. Med. 88, 470–476 (1990).

    CAS  Article  Google Scholar 

  12. 12

    Garty, B. Z. et al. Pulmonary function in children with progressive systemic sclerosis. Pediatrics 88, 1161–1167 (1991).

    CAS  PubMed  Google Scholar 

  13. 13

    Seely, J. M., Jones, L. T., Wallace, C., Sherry, D. & Effmann, E. L. Systemic sclerosis: using high-resolution CT to detect lung disease in children. AJR Am. J. Roentgenol. 170, 691–697 (1998).

    CAS  Article  Google Scholar 

  14. 14

    Panigada, S. et al. HRCT and pulmonary function tests in monitoring of lung involvement in juvenile systemic sclerosis. Pediatr. Pulmonol. 44, 1226–1234 (2009).

    Article  Google Scholar 

  15. 15

    BAL Cooperative Group Steering Committee. Bronchoalveolar lavage constituents in healthy individuals, idiopathic pulmonary fibrosis, and selected comparison groups. Am. Rev. Respir. Dis. 141, S169–S202 (1990).

  16. 16

    Witt, C. et al. Pulmonary involvement in diffuse cutaneous systemic sclerosis: broncheoalveolar fluid granulocytosis predicts progression of fibrosing alveolitis. Ann. Rheum. Dis. 58, 635–640 (1999).

    CAS  Article  Google Scholar 

  17. 17

    Strange, C. et al. Bronchoalveolar lavage and response to cyclophosphamide in scleroderma interstitial lung disease. Am. J. Respir. Crit. Care Med. 177, 91–98 (2008).

    CAS  Article  Google Scholar 

  18. 18

    Galie, N. et al. Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur. Respir. J. 34, 1219–1263 (2009).

    CAS  Article  Google Scholar 

  19. 19

    Williams, M. H. et al. Role of N-terminal brain natriuretic peptide (N-TproBNP) in scleroderma-associated pulmonary arterial hypertension. Eur. Heart J. 27, 1485–1494 (2006).

    CAS  Article  Google Scholar 

  20. 20

    Meune, C., Vignaux, O., Kahan, A. & Allanore, Y. Heart involvement in systemic sclerosis: evolving concept and diagnostic methodologies. Arch. Cardiovasc. Dis. 103, 46–52 (2010).

    Article  Google Scholar 

  21. 21

    Martini, G. et al. Factors affecting survival in juvenile systemic sclerosis. Rheumatology (Oxford) 48, 119–122 (2009).

    CAS  Article  Google Scholar 

  22. 22

    Barst, R. J., Ertel, S. I., Beghetti, M. & Ivy, D. D. Pulmonary arterial hypertension: a comparison between children and adults. Eur. Respir. J. 37, 665–677 (2011).

    CAS  Article  Google Scholar 

  23. 23

    Kowal-Bielecka, O. et al. EULAR recommendations for the treatment of systemic sclerosis: a report from the EULAR Scleroderma Trials and Research group (EUSTAR). Ann. Rheum. Dis. 68, 620–628 (2009).

    CAS  Article  Google Scholar 

  24. 24

    Tissot, C., Ivy, D. D. & Beghetti, M. Medical therapy for pediatric pulmonary arterial hypertension. J. Pediatr. 157, 528–532 (2010).

    Article  Google Scholar 

  25. 25

    Wozniak, J. et al. Evaluation of heart rhythm variability and arrhythmia in children with systemic and localized scleroderma. J. Rheumatol. 36, 191–196 (2009).

    Article  Google Scholar 

  26. 26

    Sánchez-Román, J. et al. Screening for PAH in patients with systemic sclerosis: focus on Doppler echocardiography. Rheumatology (Oxford) 47 (Suppl. 5), v33–v35 (2008).

    Article  Google Scholar 

  27. 27

    Bussone, G., Bérezné, A., Pestre, V., Guillevin, L. & Mouthon, L. The scleroderma kidney: progress in risk factors, therapy, and prevention. Curr. Rheumatol. Rep. 13, 37–43 (2011).

    Article  Google Scholar 

  28. 28

    Hamaguchi, Y. Autoantibody profiles in systemic sclerosis: predictive value for clinical evaluation and prognosis. J. Dermatol. 37, 42–53 (2010).

    CAS  Article  Google Scholar 

  29. 29

    Tashkin, D. P. et al. Cyclophosphamide versus placebo in scleroderma lung disease. N. Engl. J. Med. 354, 2655–2666 (2006).

    CAS  Article  Google Scholar 

  30. 30

    Au, K., Khanna, D., Clements, P. J., Furst, D. E. & Tashkin, D. P. Current concepts in disease-modifying therapy for systemic sclerosis-associated interstitial lung disease: lessons from clinical trials. Curr. Rheumatol. Rep. 11, 111–119 (2009).

    CAS  Article  Google Scholar 

  31. 31

    Khanna, D., Furst, D. E., Clements, P. J., Tashkin, D. P. & Eckman, M. H. Oral cyclophosphamide for active scleroderma lung disease: a decision analysis. Med. Decis. Making 28, 926–937 (2008).

    Article  Google Scholar 

  32. 32

    Su, R. et al. An analysis of connective tissue disease-associated interstitial lung disease at a US Tertiary Care Center: better survival in patients with systemic sclerosis. J. Rheumatol. 38, 693–711 (2011).

    Article  Google Scholar 

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Rabinovich, C. Challenges in the diagnosis and treatment of juvenile systemic sclerosis. Nat Rev Rheumatol 7, 676–680 (2011). https://doi.org/10.1038/nrrheum.2011.148

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