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Published in: Arthritis Research & Therapy 1/2011

Open Access 01-02-2011 | Research article

Histopathological cutaneous alterations in systemic sclerosis: a clinicopathological study

Authors: Jens T Van Praet, Vanessa Smith, Marc Haspeslagh, Nele Degryse, Dirk Elewaut, Filip De Keyser

Published in: Arthritis Research & Therapy | Issue 1/2011

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Abstract

Introduction

The aims of the present study were to identify histopathological parameters which are linked to local clinical skin disease at two distinct anatomical sites in systemic sclerosis (SSc) patients with skin involvement (limited cutaneous systemic sclerosis (lcSSc) or diffuse cutaneous systemic sclerosis (dcSSc)) and to determine the sensitivity of SSc specific histological alterations, focusing on SSc patients without clinical skin involvement (limited SSc (lSSc)).

Methods

Histopathological alterations were systematically scored in skin biopsies of 53 consecutive SSc patients (dorsal forearm and upper inner arm) and 18 controls (upper inner arm). Clinical skin involvement was evaluated using the modified Rodnan skin score. In patients with lcSSc or dcSSc, associations of histopathological parameters with local clinical skin involvement were determined by generalised estimation equation modelling.

Results

The hyalinised collagen score, the myofibroblast score, the mean epidermal thickness, the mononuclear cellular infiltration and the frequency of focal exocytosis differed significantly between biopsies with and without local clinical skin involvement. Except for mononuclear cellular infiltration, all of the continuous parameters correlated with the local clinical skin score at the dorsal forearm. Parakeratosis, myofibroblasts and intima proliferation were present in a minority of the SSc biopsies, but not in controls. No differences were found between lSSc and controls.

Conclusions

Several histopathological parameters are linked to local clinical skin disease. SSc-specific histological alterations have a low diagnostic sensitivity.
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Literature
1.
go back to reference Denton CP, Black CM, Abraham DJ: Mechanisms and consequences of fibrosis in systemic sclerosis. Nat Clin Pract Rheumatol. 2006, 2: 134-144. 10.1038/ncprheum0115.CrossRefPubMed Denton CP, Black CM, Abraham DJ: Mechanisms and consequences of fibrosis in systemic sclerosis. Nat Clin Pract Rheumatol. 2006, 2: 134-144. 10.1038/ncprheum0115.CrossRefPubMed
2.
go back to reference Akesson A, Fiori G, Krieg T, van den Hoogen FH, Seibold JR: Assessment of skin, joint, tendon and muscle involvement. Clin Exp Rheumatol. 2003, 21: S5-S8.PubMed Akesson A, Fiori G, Krieg T, van den Hoogen FH, Seibold JR: Assessment of skin, joint, tendon and muscle involvement. Clin Exp Rheumatol. 2003, 21: S5-S8.PubMed
3.
go back to reference LeRoy EC, Medsger TA: Criteria for the classification of early systemic sclerosis. J Rheumatol. 2001, 28: 1573-1576.PubMed LeRoy EC, Medsger TA: Criteria for the classification of early systemic sclerosis. J Rheumatol. 2001, 28: 1573-1576.PubMed
4.
go back to reference Koenig M, Joyal F, Fritzler MJ, Roussin A, Abrahamowicz M, Boire G, Goulet JR, Rich E, Grodzicky T, Raymond Y, Senécal JL: Autoantibodies and microvascular damage are independent predictive factors for the progression of Raynaud's phenomenon to systemic sclerosis: a twenty-year prospective study of 586 patients, with validation of proposed criteria for early systemic sclerosis. Arthritis Rheum. 2008, 58: 3902-3912. 10.1002/art.24038.CrossRefPubMed Koenig M, Joyal F, Fritzler MJ, Roussin A, Abrahamowicz M, Boire G, Goulet JR, Rich E, Grodzicky T, Raymond Y, Senécal JL: Autoantibodies and microvascular damage are independent predictive factors for the progression of Raynaud's phenomenon to systemic sclerosis: a twenty-year prospective study of 586 patients, with validation of proposed criteria for early systemic sclerosis. Arthritis Rheum. 2008, 58: 3902-3912. 10.1002/art.24038.CrossRefPubMed
5.
go back to reference Smith V, Van Praet JT, Vandooren B, Van der Cruyssen B, Naeyaert JM, Decuman S, Elewaut D, De Keyser F: Rituximab in diffuse cutaneous systemic sclerosis: an open-label clinical and histopathological study. Ann Rheum Dis. 2010, 69: 193-197. 10.1136/ard.2008.095463.CrossRefPubMed Smith V, Van Praet JT, Vandooren B, Van der Cruyssen B, Naeyaert JM, Decuman S, Elewaut D, De Keyser F: Rituximab in diffuse cutaneous systemic sclerosis: an open-label clinical and histopathological study. Ann Rheum Dis. 2010, 69: 193-197. 10.1136/ard.2008.095463.CrossRefPubMed
6.
go back to reference Nash RA, McSweeney PA, Crofford LJ, Abidi M, Chen CS, Godwin JD, Gooley TA, Holmberg L, Henstorf G, LeMaistre CF, Mayes MD, McDonagh KT, McLaughlin B, Molitor JA, Nelson JL, Shulman H, Storb R, Viganego F, Wener MH, Seibold JR, Sullivan KM, Furst DE: High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for severe systemic sclerosis: long-term follow-up of the US multicenter pilot study. Blood. 2007, 110: 1388-1396. 10.1182/blood-2007-02-072389.CrossRefPubMedPubMedCentral Nash RA, McSweeney PA, Crofford LJ, Abidi M, Chen CS, Godwin JD, Gooley TA, Holmberg L, Henstorf G, LeMaistre CF, Mayes MD, McDonagh KT, McLaughlin B, Molitor JA, Nelson JL, Shulman H, Storb R, Viganego F, Wener MH, Seibold JR, Sullivan KM, Furst DE: High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for severe systemic sclerosis: long-term follow-up of the US multicenter pilot study. Blood. 2007, 110: 1388-1396. 10.1182/blood-2007-02-072389.CrossRefPubMedPubMedCentral
7.
go back to reference Kissin EY, Merkel PA, Lafyatis R: Myofibroblasts and hyalinized collagen as markers of skin disease in systemic sclerosis. Arthritis Rheum. 2006, 54: 3655-3660. 10.1002/art.22186.CrossRefPubMed Kissin EY, Merkel PA, Lafyatis R: Myofibroblasts and hyalinized collagen as markers of skin disease in systemic sclerosis. Arthritis Rheum. 2006, 54: 3655-3660. 10.1002/art.22186.CrossRefPubMed
8.
go back to reference Smith V, Pizzorni C, De Keyser F, Decuman S, Van Praet JT, Deschepper E, Sulli A, Cutolo M: Reliability of the qualitative and semiquantitative nailfold videocapillaroscopy assessment in a systemic sclerosis cohort: a two-centre study. Ann Rheum Dis. 2010, 69: 1092-1096. 10.1136/ard.2009.115568.CrossRefPubMed Smith V, Pizzorni C, De Keyser F, Decuman S, Van Praet JT, Deschepper E, Sulli A, Cutolo M: Reliability of the qualitative and semiquantitative nailfold videocapillaroscopy assessment in a systemic sclerosis cohort: a two-centre study. Ann Rheum Dis. 2010, 69: 1092-1096. 10.1136/ard.2009.115568.CrossRefPubMed
9.
go back to reference LeRoy EC, Black C, Fleischmajer R, Jablonska S, Krieg T, Medsger TA, Rowell N, Wollheim F: Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol. 1988, 15: 202-205.PubMed LeRoy EC, Black C, Fleischmajer R, Jablonska S, Krieg T, Medsger TA, Rowell N, Wollheim F: Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol. 1988, 15: 202-205.PubMed
10.
go back to reference Clements PJ, Lachenbruch PA, Seibold JR, Zee B, Steen VD, Brennan P, Silman AJ, Allegar N, Varga J, Massa M, et al: Skin thickness score in systemic sclerosis: an assessment of interobserver variability in 3 independent studies. J Rheumatol. 1993, 20: 1892-1896.PubMed Clements PJ, Lachenbruch PA, Seibold JR, Zee B, Steen VD, Brennan P, Silman AJ, Allegar N, Varga J, Massa M, et al: Skin thickness score in systemic sclerosis: an assessment of interobserver variability in 3 independent studies. J Rheumatol. 1993, 20: 1892-1896.PubMed
11.
go back to reference Montgomery H, O'Leary PA, Ragsdale WE: Dermatohistopathology of various types of scleroderma. AMA Arch Derm. 1957, 75: 78-87.CrossRefPubMed Montgomery H, O'Leary PA, Ragsdale WE: Dermatohistopathology of various types of scleroderma. AMA Arch Derm. 1957, 75: 78-87.CrossRefPubMed
12.
go back to reference Prescott RJ, Freemont AJ, Jones CJ, Hoyland J, Fielding P: Sequential dermal microvascular and perivascular changes in the development of scleroderma. J Pathol. 1992, 166: 255-263. 10.1002/path.1711660307.CrossRefPubMed Prescott RJ, Freemont AJ, Jones CJ, Hoyland J, Fielding P: Sequential dermal microvascular and perivascular changes in the development of scleroderma. J Pathol. 1992, 166: 255-263. 10.1002/path.1711660307.CrossRefPubMed
13.
go back to reference Torres JE, Sanchez JL: Histopathologic differentiation between localized and systemic scleroderma. Am J Dermatopathol. 1998, 20: 242-245. 10.1097/00000372-199806000-00003.CrossRefPubMed Torres JE, Sanchez JL: Histopathologic differentiation between localized and systemic scleroderma. Am J Dermatopathol. 1998, 20: 242-245. 10.1097/00000372-199806000-00003.CrossRefPubMed
14.
go back to reference Roumm AD, Whiteside TL, Medsger TA, Rodnan GP: Lymphocytes in the skin of patients with progressive systemic sclerosis: quantification, subtyping, and clinical correlations. Arthritis Rheum. 1984, 27: 645-653. 10.1002/art.1780270607.CrossRefPubMed Roumm AD, Whiteside TL, Medsger TA, Rodnan GP: Lymphocytes in the skin of patients with progressive systemic sclerosis: quantification, subtyping, and clinical correlations. Arthritis Rheum. 1984, 27: 645-653. 10.1002/art.1780270607.CrossRefPubMed
15.
go back to reference Fleming JN, Shulman HM, Nash RA, Johnson PY, Wight TN, Gown A, Schwartz SM: Cutaneous chronic graft-versus-host disease does not have the abnormal endothelial phenotype or vascular rarefaction characteristic of systemic sclerosis. PLoS One. 2009, 4: e6203-10.1371/journal.pone.0006203.CrossRefPubMedPubMedCentral Fleming JN, Shulman HM, Nash RA, Johnson PY, Wight TN, Gown A, Schwartz SM: Cutaneous chronic graft-versus-host disease does not have the abnormal endothelial phenotype or vascular rarefaction characteristic of systemic sclerosis. PLoS One. 2009, 4: e6203-10.1371/journal.pone.0006203.CrossRefPubMedPubMedCentral
16.
go back to reference Rongioletti F, Gambini C, Micalizzi C, Pastorino A, Rebora A: Mucin deposits in morphea and systemic scleroderma. Dermatology. 1994, 189: 157-158. 10.1159/000246821.CrossRefPubMed Rongioletti F, Gambini C, Micalizzi C, Pastorino A, Rebora A: Mucin deposits in morphea and systemic scleroderma. Dermatology. 1994, 189: 157-158. 10.1159/000246821.CrossRefPubMed
18.
go back to reference Ackerman AB: Histologic Diagnosis of Inflammatory Skin Diseases: An Algorithmic Method Based on Pattern Analysis. 1997, Baltimore: Williams & Wilkins, 2 Ackerman AB: Histologic Diagnosis of Inflammatory Skin Diseases: An Algorithmic Method Based on Pattern Analysis. 1997, Baltimore: Williams & Wilkins, 2
19.
go back to reference Baeten D, Demetter P, Cuvelier C, Van Den Bosch F, Kruithof E, Van Damme N, Verbruggen G, Mielants H, Veys EM, De Keyser F: Comparative study of the synovial histology in rheumatoid arthritis, spondyloarthropathy, and osteoarthritis: influence of disease duration and activity. Ann Rheum Dis. 2000, 59: 945-953. 10.1136/ard.59.12.945.CrossRefPubMedPubMedCentral Baeten D, Demetter P, Cuvelier C, Van Den Bosch F, Kruithof E, Van Damme N, Verbruggen G, Mielants H, Veys EM, De Keyser F: Comparative study of the synovial histology in rheumatoid arthritis, spondyloarthropathy, and osteoarthritis: influence of disease duration and activity. Ann Rheum Dis. 2000, 59: 945-953. 10.1136/ard.59.12.945.CrossRefPubMedPubMedCentral
20.
go back to reference Furst D, Khanna D, Matucci-Cerinic M, Clements P, Steen V, Pope J, Merkel P, Foeldvari I, Seibold J, Pittrow D, Polisson R, Strand V: Systemic sclerosis: continuing progress in developing clinical measures of response. J Rheumatol. 2007, 34: 1194-1200.PubMed Furst D, Khanna D, Matucci-Cerinic M, Clements P, Steen V, Pope J, Merkel P, Foeldvari I, Seibold J, Pittrow D, Polisson R, Strand V: Systemic sclerosis: continuing progress in developing clinical measures of response. J Rheumatol. 2007, 34: 1194-1200.PubMed
21.
go back to reference Fitzpatrick TB, Wolff K, Access Medicine: Fitzpatrick's Dermatology in General Medicine. 2008, New York: McGraw-Hill Medical, 7 Fitzpatrick TB, Wolff K, Access Medicine: Fitzpatrick's Dermatology in General Medicine. 2008, New York: McGraw-Hill Medical, 7
22.
go back to reference Aden N, Shiwen X, Aden D, Black C, Nuttall A, Denton CP, Leask A, Abraham D, Stratton R: Proteomic analysis of scleroderma lesional skin reveals activated wound healing phenotype of epidermal cell layer. Rheumatology (Oxford). 2008, 47: 1754-1760. 10.1093/rheumatology/ken370.CrossRef Aden N, Shiwen X, Aden D, Black C, Nuttall A, Denton CP, Leask A, Abraham D, Stratton R: Proteomic analysis of scleroderma lesional skin reveals activated wound healing phenotype of epidermal cell layer. Rheumatology (Oxford). 2008, 47: 1754-1760. 10.1093/rheumatology/ken370.CrossRef
Metadata
Title
Histopathological cutaneous alterations in systemic sclerosis: a clinicopathological study
Authors
Jens T Van Praet
Vanessa Smith
Marc Haspeslagh
Nele Degryse
Dirk Elewaut
Filip De Keyser
Publication date
01-02-2011
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2011
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar3267

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