Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Systemic Sclerosis Workup

  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Dirk M Elston, MD  more...
 
Updated: Jun 02, 2016
 

Laboratory Studies

The following findings may be found with laboratory studies:

  • Increased erythrocyte sedimentation rate
  • Thrombocytopenia
  • Hypergammaglobulinemia
  • Microangiopathic hemolytic anemia
  • Increased creatine phosphokinase levels in patients with muscle involvement
  • Increased urea and creatinine levels in patients with kidney involvement
  • C-reactive protein: The nonspecific inflammatory marker C-reactive protein was found elevated in about one quarter of patients with systemic sclerosis, especially early disease, in whom it correlated with disease activity, severity, poor pulmonary function, and shorter survival. [24]
Next

Imaging Studies

Chest radiographs may show normal findings in 5-10% of the patients, even when the patients have respiratory tract symptoms. In approximately 30-60% of patients, fibrosis of the basal parts of the lungs is observed. Occasionally, pictures of diffuse ground-glass and honeycomb lung patterns are observed. In patients with honeycomb lung patterns, changes are irreversible. These changes can be an important feature of patient's response to treatment.

Bone radiography reveals generalized osteopenia, which most commonly affects the hands. Intra-articular calcifications often are observed.

High-resolution computed tomography (HRCT) and scintigraphy reveal thickening of the alveolar walls and intestinal tissue and honeycomb-appearing lungs.

Gastrointestinal tract changes may be depicted. Scintigraphy of the esophagus may reveal a disturbance of the esophageal passage.[25] Manometric esophageal changes may be observed during invasive examination. Upper gastrointestinal tract evaluation should be performed only in systemic sclerosis, but not in morphea.[26]

Cardiac and pulmonary vascular involvement in systemic sclerosis should be evaluated. Cardiac abnormalities may be assessed by Doppler echocardiography.[27] Left- and right-sided heart diseases were found to be common in persons with systemic sclerosis. A few patients had a restrictive mitral flow pattern, possibly due to primary cardiac involvement of systemic sclerosis. Diastolic dysfunction is the most common cardiac finding.[28]

Because cardiac involvement is one of the major problems in systemic sclerosis, evaluation of ventricular function using echocardiographic strain imaging should be considered, because it appears to be useful to detect subclinical cardiac involvement in systemic sclerosis patients with normal standard echocardiographic and tissue Doppler velocity findings.[29]

Since the initial changes in systemic sclerosis are believed to involve microcirculation, its evaluation using laser Doppler flowmetry in the distal portion of the upper extremity has been advocated.[30]

Previous
Next

Other Tests

With bronchoalveolar lavage (BAL), abnormal numbers of granulocytes, particularly neutrophils and eosinophils are present in BAL fluid. In addition, the concentration of vascular endothelial growth factor may be low.[31]

Lung function tests reveal ventilation-perfusion changes, including the following:

  • Reduced carbon monoxide diffusion capacity
  • A reduced partial pressure of oxygen, with a normal or low partial pressure of carbon dioxide
  • Restrictive ventilatory defect, with reductions in pulmonary compliance, vital capacity, and total lung capacity
  • Decreased diffusion capacity of carbon monoxide transfer factor (DLCO) levels, which is a measure of diffusion capacity

The gas transfer measurement (KCO), adjusted for alveolar volume, is also reduced.

Heart changes, including myocardial disease, pericardial problems, conduction system disease, and arrhythmias, can be observed with the following tests:

  • Electrocardiography (ECG)
  • Holter 24-hour monitoring
  • Doppler ultrasonography (US)

Exophthalmos, macroglossia, and/or gigantism may be present, with increased polyphasic potentials of normal or decreased amplitude.

Antihistone antibodies can be observed in the course of systemic sclerosis, but they are not characteristic. The following antinuclear antibodies (ANAs) are characteristic of scleroderma:

  • Antibodies against topoisomerase I DNA (Scl 70) are detected in the serum of patients with systemic sclerosis. The antibodies are detected in two thirds of patients with dSSc and interstitial lung fibrosis.
  • Anticentromere antibodies (ACAs) are most commonly detected in patients with lSSc; in these patients, changes in the heart, kidneys, and lungs (without fibrosis) are observed less frequently than in other patients.

ANAs can be detected in the course of systemic sclerosis. ANAs include antibodies against fibrillarin, a 34-kd protein of ribonucleoprotein U3 RNP; antibodies against the ribonucleoprotein nucleolar 7-2 RNA protein particle Th RNP; and antibodies to 20-110-kd proteins related to preribosomes (PM-Scl). Anti-PM/Scl antibodies are seen in roughly 24% of patients with polymyositis/systemic sclerosis overlap syndrome. They are also found in 3-10% of systemic sclerosis patients.[32, 33] The spectrum of systemic sclerosis-associated ANA differs in patients with and without cutaneous involvement.[34] ANA serum levels in patients with systemic sclerosis are not correlated with disease activity.

Elevated high-sensitivity C-reactive protein appears related to the occurrence of antimitochondrial antibody in these patients.[35]

With capillary microscopy, enlarged capillaries are observed in all 3 portions of the capillary nail fold–arterial, apical, and venous– and especially at the edge of the nail fold. Adjacent areas are avascular.

Spirometry demonstrates functional lung disturbances. In approximately 70% of patients, the DLCO is decreased.

Previous
Next

Histologic Findings

In the active indurative phase, a loss of rete ridges occurs, epidermal skin appendages atrophy, and collagen fibers in the reticular dermis appear broad and hyalinized. A loss of space between collagen bundles is noted. Mononuclear cells, mostly T cells, form a variable perivascular infiltrate in the deep dermis and subcutis. Later, sclerotic changes predominate. The number of adnexal structures is reduced, and a loss of periadnexal fat is noted.

In one study, progressive systemic sclerosis histologic changes were systematically scored in skin biopsy specimens of dorsal forearm and upper inner arm in 53 consecutive patients and controls. The amount of hyalinized collagen, myofibroblasts, mean epidermal thickness, the mononuclear cellular infiltration, and the frequency of focal exocytosis varied significantly between those with and those without local clinical skin involvement.[36]

Previous
 
 
Contributor Information and Disclosures
Author

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School; Visiting Professor, Rutgers University School of Public Affairs and Administration

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, New York Academy of Medicine, American Academy of Dermatology, American College of Physicians, Sigma Xi

Disclosure: Nothing to disclose.

Coauthor(s)

Anna Zalewska, MD, PhD Professor of Dermatology and Venereology, Psychodermatology Department, Chair of Clinical Immunology and Microbiology, Medical University of Lodz, Poland

Disclosure: Nothing to disclose.

Specialty Editor Board

David F Butler, MD Section Chief of Dermatology, Central Texas Veterans Healthcare System; Professor of Dermatology, Texas A&M University College of Medicine; Founding Chair, Department of Dermatology, Scott and White Clinic

David F Butler, MD is a member of the following medical societies: American Medical Association, Alpha Omega Alpha, Association of Military Dermatologists, American Academy of Dermatology, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Phi Beta Kappa

Disclosure: Nothing to disclose.

Jeffrey P Callen, MD Professor of Medicine (Dermatology), Chief, Division of Dermatology, University of Louisville School of Medicine

Jeffrey P Callen, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, American College of Rheumatology

Disclosure: Received income in an amount equal to or greater than $250 from: XOMA; Biogen/IDEC; Novartis; Janssen Biotech, Abbvie, CSL pharma<br/>Received honoraria from UpToDate for author/editor; Received honoraria from JAMA Dermatology for associate editor and intermittent author; Received royalty from Elsevier for book author/editor; Received dividends from trust accounts, but I do not control these accounts, and have directed our managers to divest pharmaceutical stocks as is fiscally prudent from Stock holdings in various trust accounts include some pharmaceutical companies and device makers for i inherited these trust accounts; for: Celgene; Pfizer; 3M; Johnson and Johnson; Merck; Abbott Laboratories; AbbVie; Procter and Gamble; Amgen.

Chief Editor

Dirk M Elston, MD Professor and Chairman, Department of Dermatology and Dermatologic Surgery, Medical University of South Carolina College of Medicine

Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Mark W Cobb, MD Consulting Staff, WNC Dermatological Associates

Mark W Cobb, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Society of Dermatopathology

Disclosure: Nothing to disclose.

Acknowledgements

Bozena Dziankowska-Bartkowiak, MD, PhD Consulting Staff, Department of Dermatology, University Hospital, Medical University of Lodz, Poland

Disclosure: Nothing to disclose.

Anna Sysa-Jedrzejowska, MD, PhD Head, Professor, Department of Dermatology and Venereology, Medical University of Lodz, Poland

Disclosure: Nothing to disclose.

References
  1. Park JS, Park MC, Song JJ, Park YB, Lee SK, Lee SW. Application of the 2013 ACR/EULAR classification criteria for systemic sclerosis to patients with Raynaud's phenomenon. Arthritis Res Ther. 2015 Mar 22. 17(1):77. [Medline]. [Full Text].

  2. Sakkas LI. New developments in the pathogenesis of systemic sclerosis. Autoimmunity. 2005 Mar. 38(2):113-6. [Medline].

  3. Nguyen C, Berezne A, Baubet T, et al. Association of Gender with Clinical Expression, Quality of Life, Disability, and Depression and Anxiety in Patients with Systemic Sclerosis. PLoS One. 2011 Mar 9. 6(3):e17551. [Medline]. [Full Text].

  4. Mathai SC, Hummers LK, Champion HC, et al. Survival in pulmonary hypertension associated with the scleroderma spectrum of diseases: impact of interstitial lung disease. Arthritis Rheum. 2009 Feb. 60(2):569-77. [Medline].

  5. Alba MA, Velasco C, Simeón CP, Fonollosa V, Trapiella L, Egurbide MV, et al. Early- versus Late-Onset Systemic Sclerosis: Differences in Clinical Presentation and Outcome in 1037 Patients. Medicine (Baltimore). 2014 Mar. 93(2):73-81. [Medline].

  6. Hissaria P, Roberts-Thomson PJ, Lester S, Ahern MJ, Smith MD, Walker JG. Cigarette smoking in patients with systemic sclerosis - reduces overall survival. Arthritis Rheum. 2011 Mar 24. [Medline].

  7. Jung S, Martin T, Schmittbuhl M, Huck O. The spectrum of orofacial manifestations in systemic sclerosis: a challenging management. Oral Dis. 2016 May 19. [Medline].

  8. Mozzetta A, Antinone V, Alfani S, et al. Mental health in patients with systemic sclerosis: a controlled investigation. J Eur Acad Dermatol Venereol. 2008 Mar. 22(3):336-40. [Medline].

  9. Kwakkenbos L, van Lankveld WG, Vonk MC, Becker ES, van den Hoogen FH, van den Ende CH. Disease-related and psychosocial factors associated with depressive symptoms in patients with systemic sclerosis, including fear of progression and appearance self-esteem. J Psychosom Res. 2012 Mar. 72(3):199-204. [Medline].

  10. Hudson M, Steele R, Taillefer S, Baron M; Canadian Scleroderma Research. Quality of life in systemic sclerosis: Psychometric properties of the World Health Organization Disability Assessment Schedule II. Arthritis Rheum. 2008 Jan 31. 59(2):270-278. [Medline].

  11. Ungprasert P, Srivali N, Kittanamongkolchai W. Systemic sclerosis and risk of venous thromboembolism: A systematic review and meta-analysis. Mod Rheumatol. 2015 Apr 7. 1-17. [Medline].

  12. Malcarne VL, Hansdottir I, McKinney A. Medical signs and symptoms associated with disability, pain, and psychosocial adjustment in systemic sclerosis. J Rheumatol. 2007 Feb. 34(2):359-67. [Medline].

  13. Jarzabek-Chorzelska M, Blaszczyk M, Jablonska S, Chorzelski T, Kumar V, Beutner EH. Scl 70 antibody--a specific marker of systemic sclerosis. Br J Dermatol. 1986 Oct. 115(4):393-401. [Medline].

  14. Spencer-Green G, Alter D, Welch HG. Test performance in systemic sclerosis: anti-centromere and anti-Scl-70 antibodies. Am J Med. 1997 Sep. 103(3):242-8. [Medline].

  15. Dogan S, Akdogan A, Atakan N. Nailfold capillaroscopy in systemic sclerosis: Is there any difference between videocapillaroscopy and dermatoscopy?. Skin Res Technol. 2013 Mar 25. [Medline].

  16. Aozasa N, Asano Y, Ashida R, et al. Systemic sclerosis with an unusual rapid development of huge calcinosis (tumoral calcinosis). J Dermatol. 2011 Mar 2. [Medline].

  17. Wielosz E, Borys O, Zychowska I, Majdan M. Gastrointestinal involvement in patients with systemic sclerosis. Pol Arch Med Wewn. 2010 Apr. 120(4):132-6. [Medline].

  18. Schieir O, Thombs BD, Hudson M, Boivin JF, Steele R, Bernatsky S, et al. Prevalence, severity, and clinical correlates of pain in patients with systemic sclerosis. Arthritis Care Res (Hoboken). 2010 Mar. 62(3):409-17. [Medline].

  19. Troldborg A, Nielsen BD, Kolstad HA, Olesen AB, Søndergaard KH. [Silica exposure and the risk of systemic sclerosis.]. Ugeskr Laeger. 2013 Feb 18. 175(8):501-503. [Medline].

  20. Kawakami T, Tsutsumi Y, Soma Y. Limited cutaneous systemic sclerosis induced by paclitaxel in a patient with breast cancer. Arch Dermatol. 2009 Jan. 145(1):97-8. [Medline].

  21. Khoo JJ, Pratt EJ. Phaeochromocytoma mimicking scleroderma. Int J Endocrinol. 2011. 2011:917453. [Medline]. [Full Text].

  22. Itoh M, Yanaba K, Kobayashi T, Nakagawa H. Taxane-induced scleroderma. Br J Dermatol. 2007 Feb. 156(2):363-7. [Medline].

  23. Chen JK, Chung L, Fiorentino DF. Characterization of patients with clinical overlap of morphea and systemic sclerosis: A case series. J Am Acad Dermatol. 2016 Jun. 74 (6):1272-4. [Medline].

  24. Muangchan C, Harding S, Khimdas S, Bonner A, Baron M, Pope J. C - reactive protein (CRP) is associated with high disease activity in systemic sclerosis: results from the Canadian Scleroderma Research Group (CSRG). Arthritis Care Res (Hoboken). 2012 May 3. [Medline].

  25. Waszczykowska E, Kukulski K, Sysa-Jedrzejowska A, Dziankowska-Bartkowiak B, Gierach D, Omulecki A. Evaluation of esophageal passage in selected connective tissue diseases. J Med. 1997. 28(3-4):163-74. [Medline].

  26. Arif T, Masood Q, Singh J, Hassan I. Assessment of esophageal involvement in systemic sclerosis and morphea (localized scleroderma) by clinical, endoscopic, manometric and pH metric features: a prospective comparative hospital based study. BMC Gastroenterol. 2015 Feb 15. 15(1):24. [Medline]. [Full Text].

  27. de Groote P, Gressin V, Hachulla E, et al. Evaluation of cardiac abnormalities by Doppler echocardiography in a large nationwide multicentric cohort of patients with systemic sclerosis. Ann Rheum Dis. 2008 Jan. 67(1):31-6. [Medline].

  28. Foocharoen C, Pussadhamma B, Mahakkanukrauh A, Suwannaroj S, Nanagara R. Asymptomatic cardiac involvement in Thai systemic sclerosis: prevalence and clinical correlations with non-cardiac manifestations (preliminary report). Rheumatology (Oxford). 2015 Apr 10. [Medline].

  29. Kepez A, Akdogan A, Sade LE, et al. Detection of Subclinical Cardiac Involvement in Systemic Sclerosis by Echocardiographic Strain Imaging. Echocardiography. 2008 Feb. 25(2):191-197. [Medline].

  30. Waszczykowska A, Gos R, Waszczykowska E, Dziankowska-Bartkowiak B, Jurowski P. Assessment of skin microcirculation by laser Doppler flowmetry in systemic sclerosis patients. Postepy Dermatol Alergol. 2014 Feb. 31(1):6-11. [Medline]. [Full Text].

  31. De Santis M, Bosello SL, Capoluongo E, Inzitari R, Peluso G, Lulli P, et al. A vascular endothelial growth factor deficiency characterises scleroderma lung disease. Ann Rheum Dis. 2012 Mar 27. [Medline].

  32. Blaszczyk M, Jarzabek-Chorzelska M, Jablonska S, et al. Autoantibodies to nucleolar antigens in systemic scleroderma: clinical correlations. Br J Dermatol. 1990 Oct. 123(4):421-30. [Medline].

  33. Bruns M, Herrmann K, Haustein UF. Immunologic parameters in systemic sclerosis. Int J Dermatol. 1994 Jan. 33(1):25-32. [Medline].

  34. Van Praet JT, Smith V, Haspeslagh M, Degryse N, Elewaut D, De Keyser F. Histopathological cutaneous alterations in systemic sclerosis: a clinicopathological study. Arthritis Res Ther. 2011 Feb 28. 13(1):R35. [Medline].

  35. Ohtsuka T. Relation between elevated high-sensitivity C-reactive protein and anti-mitochondria antibody in patients with systemic sclerosis. J Dermatol. 2008 Feb. 35(2):70-5. [Medline].

  36. Van Praet JT, Van Steendam K, Smith V, et al. Specific anti-nuclear antibodies in systemic sclerosis patients with and without skin involvement: an extended methodological approach. Rheumatology (Oxford). 2011 Feb 17. [Medline].

  37. García de la Peña Lefebvre P, Nishishinya MB, Pereda CA, Loza E, Sifuentes Giraldo WA, Román Ivorra JA, et al. Efficacy of Raynaud's phenomenon and digital ulcer pharmacological treatment in systemic sclerosis patients: a systematic literature review. Rheumatol Int. 2015 Apr 1. [Medline].

  38. Wigley FM, Korn JH, Csuka ME, et al. Oral iloprost treatment in patients with Raynaud's phenomenon secondary to systemic sclerosis: a multicenter, placebo-controlled, double-blind study. Arthritis Rheum. 1998 Apr. 41(4):670-7. [Medline].

  39. Krasagakis K, Dippel E, Ramaker J, Owsianowski M, Orfanos CE. Management of severe scleroderma with long-term extracorporeal photopheresis. Dermatology. 1998. 196(3):309-15. [Medline].

  40. Seyger MM, van den Hoogen FH, van Vlijmen-Willems IM, van de Kerkhof PC, de Jong EM. Localized and systemic scleroderma show different histological responses to methotrexate therapy. J Pathol. 2001 Apr. 193(4):511-6. [Medline].

  41. Mendoza FA, Nagle SJ, Lee JB, Jimenez SA. A Prospective Observational Study of Mycophenolate Mofetil Treatment in Progressive Diffuse Cutaneous Systemic Sclerosis of Recent Onset. J Rheumatol. 2012 Apr 1. [Medline].

  42. Hider SL, Woodhead M, Taylor PM, Bruce IN. Lung fibrosis in systemic sclerosis treated with a combination of ciclosporin and azathioprine. Clin Exp Rheumatol. 2006 Mar-Apr. 24(2):215. [Medline].

  43. Valentini G, Paone C, La Montagna G, et al. Low-dose intravenous cyclophosphamide in systemic sclerosis: an open prospective efficacy study in patients with early diffuse disease. Scand J Rheumatol. 2006 Jan-Feb. 35(1):35-8. [Medline].

  44. Varai G, Earle L, Jimenez SA, Steiner RM, Varga J. A pilot study of intermittent intravenous cyclophosphamide for the treatment of systemic sclerosis associated lung disease. J Rheumatol. 1998 Jul. 25(7):1325-9. [Medline].

  45. Furukawa S, Yasuda S, Amengual O, Horita T, Atsumi T, Koike T. Protective effect of pravastatin on vascular endothelium in patients with systemic sclerosis: a pilot study. Ann Rheum Dis. 2006 Aug. 65(8):1118-20. [Medline].

  46. Blagojevic J, Matucci-Cerinic M. Are statins useful for treating vascular involvement in systemic sclerosis?. Nat Clin Pract Rheumatol. 2009 Feb. 5(2):70-1. [Medline].

  47. Verrecchia F, Laboureau J, Verola O, et al. Skin involvement in scleroderma--where histological and clinical scores meet. Rheumatology (Oxford). 2007 May. 46(5):833-41. [Medline].

  48. Huang J, Beyer C, Palumbo-Zerr K, Zhang Y, Ramming A, Distler A, et al. Nintedanib inhibits fibroblast activation and ameliorates fibrosis in preclinical models of systemic sclerosis. Ann Rheum Dis. 2015 Apr 9. [Medline].

  49. Chung L, Fiorentino DF, Benbarak MJ, et al. Molecular framework for response to imatinib mesylate in systemic sclerosis. Arthritis Rheum. 2009 Jan 29. 60(2):584-591. [Medline].

  50. Pannu J, Asano Y, Nakerakanti S, et al. Smad1 pathway is activated in systemic sclerosis fibroblasts and is targeted by imatinib mesylate. Arthritis Rheum. 2008 Aug. 58(8):2528-37. [Medline].

  51. Halachmi S, Gabari O, Cohen S, Koren R, Amitai DB, Lapidoth M. Telangiectasis in CREST syndrome and systemic sclerosis: correlation of clinical and pathological features with response to pulsed dye laser treatment. Lasers Med Sci. 2013 Mar 14. [Medline].

  52. Dinsdale G, Murray A, Moore T, Ferguson J, Wilkinson J, Richards H, et al. A comparison of intense pulsed light and laser treatment of telangiectases in patients with systemic sclerosis: a within-subject randomized trial. Rheumatology (Oxford). 2014 Mar 28. [Medline].

  53. Scope A, Sadetzki S, Sidi Y, et al. Breast cancer and scleroderma. Skinmed. 2006 Jan-Feb. 5(1):18-24. [Medline].

  54. Riera R, Andrade LE, Souza AW, Kayser C, Yanagita ET, Trevisani VF. Lidocaine for systemic sclerosis: a double-blind randomized clinical trial. Orphanet J Rare Dis. 2011 Feb 7. 6:5. [Medline]. [Full Text].

 
Previous
Next
 
Face of 65-year old woman with systemic sclerosis and skin thickening of 20 years' duration: Note the pinched nose, taut skin with numerous telangiectasias, and retraction of the lips.
Telangiectasias affecting the face: They are pronounced and numerous, especially in the atrophic phase of the disease. Radical furrowing around the mouth is also characteristic in the later stage of the disease.
Raynaud phenomenon of the hands: Symmetrical acral vasospasm is present, with characteristic pallor, cyanosis, suffusion, and a sense of fullness and tautness.
Puffy appearance of the woman's hand in the edematous phase of early scleroderma.
In systemic sclerosis, ulceration at the tip of the finger is regarded to be secondary to ischemia.
Hand of a woman with scleroderma of several years' duration: The thickened, tight, thin skin over the fingers is the result of self-amputation of the distal phalanx due to ischemia. Moderately severe flexion contractures of the fingers are present.
In systemic sclerosis, skin hyperpigmentation of the lower legs is surrounded by areas of hypopigmentation. The result is a salt-and-pepper appearance.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.