Juvenile Systemic Sclerosis Workup
- Author: Donald A Person, MD, FAAP, FACR; Chief Editor: Harumi Jyonouchi, MD more...
In juvenile systemic sclerosis (JSSc) as in many of the systemic rheumatic diseases, inflammation may be associated with anemia, thrombocytosis and possibly eosinophilia. Therefore, obtaining routine CBC counts and erythrocyte sediment rates (ESRs) is prudent. Other early studies may include a urinalysis, chemistry survey, and ANA tests. These tests help to establish baseline values before the introduction of potentially toxic medications (see Medication).
- Early in the course of the disease, few, if any, laboratory finding abnormalities may be present. Later, mild anemia with slight thrombocytosis may be evident. Regular monitoring of these values may be warranted when a diagnosis of systemic sclerosis is suspected.
- The ESR is often normal or only mildly elevated in patients with juvenile systemic sclerosis. The largest published case series showed elevation of ESR in 34% of patients.
- Peripheral eosinophilia should alert the clinician to one of the variants of scleroderma.
- Hematuria, proteinuria, and cellular casts are an ominous sign in patients with juvenile systemic sclerosis and may represent impending renal insufficiency.
- Survey chemistry findings are useful in monitoring disease activity and drug-associated toxicities.
- Rheumatoid factor (RF) is present in 17% of patients with juvenile systemic sclerosis, slightly less than the 25% of those with adult-onset disease.
- Immunologic tests are often helpful in patients with JSSc. Patients often have a positive ANA (with a speckled staining pattern, most commonly nucleolar). The precise frequency is debated, but most experts estimate that between 81-97% of patients with JSSc have a positive ANA. Antinucleolar staining is observed almost exclusively in adult and pediatric patients with systemic sclerosis. Some of the other autoantibodies suggestive of systemic sclerosis or scleroderma that have been described include those listed below. However, note that as many as one third of patients who are diagnosed with JSSc and have positive ANA findings do not have any of the more specific autoantibodies, including the following:
- Anti-SCL 70 - Specific for topoisomerase I, found in 28-34% of cases
- Anti–RNA polymerase
- Anti-centromere - Only found in 7-8% of juvenile systemic sclerosis cases compared with 21-23% of adults systemic sclerosis cases
- Anti-RNA polymerase I or II
- Contrary to findings in adult disease, the presence of anti-topoisomerase I and anti-RNA polymerase III antibodies are not associated with poorer survival in JSSc.
- In one third of cases, quantitative immunoglobulin levels may demonstrate a mild to modest immunoglobulin G (IgG) hypergammaglobulinemia. This nonspecific polyclonal gammopathy is detectable in many chronic inflammatory and systemic rheumatic diseases. Complement levels are normal in most cases. Test results for circulating immune complexes are usually negative.
See the list below:
- Although once commonly obtained in patients with juvenile systemic sclerosis, barium swallow with small bowel follow-through has been replaced by esophageal manometry.
- High-resolution thin-cut CT (HRCT) of the lungs has been helpful in making the diagnosis and in following the progress of diffuse interstitial pneumonitis and pulmonary fibrosis in patients with juvenile systemic sclerosis.
See the list below:
- Nailfold capillaroscopy may reveal changes prior to the onset of systemic symptoms. The changes noted on nailfold capillaroscopy in patients with Raynaud phenomenon include abnormal capillary dilation (resulting from vasculopathy) or loss of nailfold capillaries.
- Although high resolution computed tomography (HRCT) remains the imaging study of choice when monitoring patients with JSSc for early evidence interstitial pneumonitis and pulmonary fibrosis, the diffusing capacity of the lung for carbon monoxide (DLCO) test is the most sensitive for detecting early evidence of pulmonary fibrosis.
- Although skin biopsies have been useful in assessing patients with systemic sclerosis for years, the results are not specific and must always be correlated with clinical features. Tests for collagen synthesis have not been consistently helpful, and their performance and interpretation requires the expertise of a research laboratory.
- Esophageal manometry is currently the study of choice for diagnosis of esophageal involvement in patient with juvenile systemic sclerosis.
See the list below:
- Early in the course of systemic sclerosis, an inflammatory reaction with subintimal vascular proliferation and an infiltration of round cells often goes unrecognized. After a varying length of time, fibrosis follows this reaction. Fibrosis characterizes the final common pathway in systemic sclerosis.
- In the skin, thinning of the epidermis occurs, with loss of rete pegs as collagens and accumulation of other matrix proteins in the dermis. Early studies made use of this feature to quantitate dermal thickness in skin biopsies and relate the degree of fibrosis with disease severity.
- Arteriolar and capillary endothelial proliferation precedes fibrosis in the visceral organs. Prognosis is related to the intensity and rapidity of fibrosis in the lungs, heart, GI tract, and kidney. Finally, atrophy ensues, and vital function is compromised.
- Humoral and cellular immunity both contribute to the pathology of systemic sclerosis, but the intimate details remain to be elucidated. The complex relationships among immune, vascular, and fibrotic perturbations may help explain the difficulties encountered in the treatment of patients with systemic sclerosis.
Johnson SR, Swiston JR, Granton JT. Prognostic factors for survival in scleroderma associated pulmonary arterial hypertension. J Rheumatol. 2008 Aug. 35(8):1584-90. [Medline].
Martini G, Foeldvari I, Russo R, Cuttica R, Eberhard A, Ravelli A, et al. Systemic sclerosis in childhood: clinical and immunologic features of 153 patients in an international database. Arthritis Rheum. 2006 Dec. 54(12):3971-8. [Medline].
[Guideline] Kowal-Bielecka O, Landewé R, Avouac J, Chwiesko S, Miniati I, Czirjak L, et al. EULAR recommendations for the treatment of systemic sclerosis: a report from the EULAR Scleroderma Trials and Research group (EUSTAR). Ann Rheum Dis. 2009 May. 68(5):620-8. [Medline].
Martini G, Vittadello F, Kasapçopur O, Magni Manzoni S, Corona F, Duarte-Salazar C, et al. Factors affecting survival in juvenile systemic sclerosis. Rheumatology (Oxford). 2009 Feb. 48(2):119-22. [Medline].
Black CM, Denton CP. Therapy of Systemic Sclerosis. Van de Putte LBA, Furst DE, Williams HJ, van Riel PLCM, eds. Therapy of Systemic Rheumatic Disorders. 1998. 495-545.
Bottoni CR, Reinker KA, Gardner RD, Person DA. Scleroderma in childhood: a 35-year history of cases and review of the literature. J Pediatr Orthop. 2000 Jul-Aug. 20(4):442-9. [Medline].
Foeldvari I. New developments in juvenile systemic and localized scleroderma. Rheum Dis Clin North Am. 2013 Nov. 39(4):905-20. [Medline].
Foeldvari I, Tyndall A, Zulian F, et al. Juvenile and young adult-onset systemic sclerosis share the same organ involvement in adulthood: data from the EUSTAR database. Rheumatology (Oxford). 2012 Oct. 51(10):1832-7. [Medline].
Foti R, Leonardi R, Rondinone R, Di Gangi M, Leonetti C, Canova M, et al. Scleroderma-like disorders. Autoimmun Rev. 2008 Feb. 7(4):331-9. [Medline].
Gerhold K, Becker MO. Nailfold capillaroscopy in juvenile rheumatic diseases: known measures, patterns and indications. Clin Exp Rheumatol. 2014 Jun 6. [Medline].
Hoeper MM. Pulmonary hypertension in collagen vascular disease. Eur Respir J. 2002 Mar. 19(3):571-6. [Medline].
Kaal SE, van Den Hoogen FH, de Jong EM, Viëtor HE. Systemic sclerosis: new insights in autoimmunity. Proc Soc Exp Biol Med. 1999 Oct. 222(1):1-8. [Medline].
LeRoy EC. Pathogenesis of Systemic Sclerosis (scleroderma). Koopman WJ, ed. Arthritis and Allied Conditions. 1997. 1481-90.
Levy BD. Eicosanoids in scleroderma: lung disease hangs in the balance. Arthritis Rheum. 2005 Dec. 52(12):3693-7. [Medline].
Nagaya N. Drug therapy of primary pulmonary hypertension. Am J Cardiovasc Drugs. 2004. 4(2):75-85. [Medline].
Poormoghim H, Lucas M, Fertig N, Medsger TA Jr. Systemic sclerosis sine scleroderma: demographic, clinical, and serologic features and survival in forty-eight patients. Arthritis Rheum. 2000 Feb. 43(2):444-51. [Medline].
Rabinovich CE. Challenges in the diagnosis and treatment of juvenile systemic sclerosis. Nat Rev Rheumatol. 2011 Oct 11. 7(11):676-80. [Medline].
Reiff A, Weinberg KI, Triche T, et al. T lymphocyte abnormalities in juvenile systemic sclerosis patients. Clin Immunol. 2013 Oct. 149(1):146-55. [Medline].
Rosenkranz ME, Agle LM, Efthimiou P, Lehman TJ. Systemic and localized scleroderma in children: current and future treatment options. Paediatr Drugs. 2006. 8(2):85-97. [Medline].
Russo RA, Katsicas MM. Clinical characteristics of children with Juvenile Systemic Sclerosis: follow-up of 23 patients in a single tertiary center. Pediatr Rheumatol Online J. 2007 May 1. 5:6. [Medline]. [Full Text].
Shimizu M, Hashida Y, Ueno K, et al. Successful treatment with bosentan for pulmonary hypertension and reduced peripheral circulation in juvenile systemic sclerosis. Pediatr Cardiol. 2011 Oct. 32(7):1040-2. [Medline].
Silver RM. Variant forms of scleroderma. Koopman WJ, ed. Arthritis and Allied Conditions. 1997. 1465-80.
Steen V. Advancements in diagnosis of pulmonary arterial hypertension in scleroderma. Arthritis Rheum. 2005 Dec. 52(12):3698-700. [Medline].
Vancheeswaran R, Black CM, David J, Hasson N, Harper J, Atherton D, et al. Childhood-onset scleroderma: is it different from adult-onset disease. Arthritis Rheum. 1996 Jun. 39(6):1041-9. [Medline].
Zulian F. Systemic sclerosis and localized scleroderma in childhood. Rheum Dis Clin North Am. 2008 Feb. 34(1):239-55; ix. [Medline].
Zulian F, Martini G. Childhood systemic sclerosis. Curr Opin Rheumatol. 2007 Nov. 19(6):592-7. [Medline].
[Guideline] Zulian F, Woo P, Athreya BH, Laxer RM, Medsger TA Jr, Lehman TJ, et al. The Pediatric Rheumatology European Society/American College of Rheumatology/European League against Rheumatism provisional classification criteria for juvenile systemic sclerosis. Arthritis Rheum. 2007 Mar 15. 57(2):203-12. [Medline].