New aspects of localized scleroderma pathogenesis: practical basis

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Abstract

BACKGROUND: Recently there has been an increase in the number of patients with scleroderma.

AIM: This study aimed to investigate the pathogenesis and course and present the immunopathogenesis of localized scleroderma (LS) or morphea.

MATERIALS AND METHODS: From 2010 to 2019, a prospective study of 77 patients with LS was conducted on the basis of the Leningrad regional center for specialized types of medical care. Based on histological examination, LS diagnosis was verified in 40 of 77 patients. Patients with LS (n = 40) were included in the first research group and were then divided into two subgroups based on the limitation period for the first symptoms of the disease: in subgroup I (n = 20), the disease manifested no later than 1.7 months before clinic visit; in subgroup II (n = 20), the limitation period was 1.5 years.

RESULTS: Patients of both subgroups (n = 40) underwent immunohistochemical (IL-2, IL-4, CD4, CD8, vimentin, Toll-like receptor – TLR7) tissue analysis and immunological blood tests to determine autoantibodies. To improve the differential diagnosis of LS, a comparative assessment of clinical manifestations and histological signs was performed in patients with LS (n = 40) and patients with clinically similar dermatoses (n = 37): annular granuloma (n = 12, 7 women and 5 men, average age 44 ± 12 years), small plaque (n = 15, 6 women and 9 men, average age 42 ± 4 years), and large plaque (n = 10, 5 women and 5 men, average age 59 ± 8 years) parapsoriasis. According to the results of the histological examination, inflammatory changes are dominant in patients with LS manifestation period of 1.7 months from the onset of the disease, while fibrotic changes are apparent in patients with a manifestation period of 1.5 years. The expressions of CD4, CD8, IL-2, and TLR7 were more pronounced in subgroup 1, while those of IL-4, CD4, and vimentin were high in subgroup 2. No autoantibodies were detected in the blood of patients with LS. The results allow us to divide the pathogenesis of LS into two phases: inflammatory and fibrotic. Immune dysregulation and fibrosis occur simultaneously, but with phase dependant predominance.

CONCLUSIONS: In the future, a detailed understanding of the pathogenesis of LS will help improve diagnostic and therapeutic algorithms and reduce the frequency of relapse and complications.

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About the authors

Denis V. Zaslavsky

St. Petersburg State Pediatric Medical University

Author for correspondence.
Email: venerology@gmail.com
ORCID iD: 0000-0001-5936-6232

MD, PhD, DSc, Professor dermatovenereology department, St. Petersburg State Pediatric Medical University

Russian Federation, St. Petersburg

A. A. Sidikov

Tashkent State Dental Institute

Email: venerology@gmail.com
ORCID iD: 0000-0002-0909-7588
Uzbekistan, Tashkent

L. V. Garyutkina

St. Petersburg State Pediatric Medical University

Email: venerology@gmail.com
Russian Federation, St. Petersburg

A. I. Sadykov

LCC “Medical clinic XXI century”

Email: venerology@gmail.com
Russian Federation, St. Petersburg

I. N. Chuprov

North-Western State Medical University na II Mechnikov

Email: venerology@gmail.com
Russian Federation, St. Petersburg

D. V. Kozlova

St. Petersburg State Pediatric Medical University

Email: venerology@gmail.com
Russian Federation, St. Petersburg

References

  1. Ananieva LP. Treatment of systemic scleroderma based on national recommendations and recommendations of the European League against rheumatism (eular). Moscow: Bionica Media; 2018:79-86. (in Russian)
  2. Rodionov AN, Nasyrov RA, Zaslavsky DV, et al. Diffuse connective tissue disease: clinical features and morphology of the skin lesions. St.Petersburg: Navoi; 2015. (in Russian)
  3. Dharamsi JW, Victor S, Aguwa N, Ahn C, Arnett F, Mayes MD, Jacobe H. Morphea in adults and children cohort III: nested case-control study–the clinical significance of autoantibodies in morphea. JAMA Dermatol. 2013;149(10):1159-65.
  4. Mayes MD. Classification and epidemiology of scleroderma. Semin Cutan Med Surg. 1998;17(1):22-6.
  5. Rodionov AN, Zaslavsky DV, Sidikow AA, Chuprov IN, Agaev RA, Skrek SV, et al. Illustrated handbook of clinical diagnosis by professor Rodionov AN. Moscow: Publishing House “Granitsa”; 2018. (in Russian)
  6. Olisova OYu, ed. Skin and Venereal Diseases. Moscow: Praktical Medicina; 2015. (in Russian)
  7. Rodionov AN, Zaslavsky DV, Sidikov AA. Clinical dermato- logy. Moscow: GEOTAR-Media; 2019. (in Russian)
  8. Dubensky VV, Nekrasova EG, Dubensky Vl V, Aleksandrova OA, Muraveva ES, Ivanova AS. Rare forms of localized scleroderma. Russian Journal of Skin and Venereal Diseases. 2019;22(1):46-50. (in Russian)
  9. Zulian F, Vallongo C, Woo P, Russo R, Ruperto N, Harper J, et al.; Juvenile Scleroderma Working Group of the Pediatric Rheumatology European Society (PRES). Localized scleroderma in childhood is not just a skin disease. Arthritis Rheum. 2005;52(9):2873-81. doi: 10.1002/art.21264
  10. Kister I, Inglese M, Laxer RM, Herbert J. Neurologic manifestations of localized scleroderma: a case report and literature review. Neurology. 2008;71(19):1538-45. doi: 10.1212/01.wnl.0000334474.88923.e3
  11. Torok KS, Li SC, Jacobe HM, Taber SF, Stevens AM, Zulian F, Lu TT. Immunopathogenesis of pediatric localized scleroderma. Front Immunol. 2019;10:908. doi: 10.3389/fimmu.2019.00908
  12. Rodionov AN, Zaslavsky DV, Chuprov IN, Nasyrov RA, Zaitsev VS, Ibragimov KU, et al. Dermatopathology of Inflammatory Skin Diseases. Tashkent: Baktria Press; 2014. (in Russian)
  13. Odonwodo A, Badri T, Hariz A. Scleroderma (Systemic Sclerosis). In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2020.
  14. Chia JJ, Lu TT. Update on macrophages and innate immunity in scleroderma. Curr Opin Rheumatol. 2015;27(6):530-6.
  15. Arisi M, Cavazzana I, Cerutti ME, Ferrari F, Carabellese N, Rossi MT, et al. Antibodies against antigens related to scleroderma in a cohort of patients with morphea. G Ital Dermatol Venereol. 2018;153(4):451-8.
  16. Khatri S, Torok KS, Mirizio E, Liu C, Astakhova K. Autoantibodies in morphea: An update. Front Immunol. 2019;10:1487. doi: 10.3389/fimmu.2019.01487
  17. Wu EY, Li SC, Torok KS, Virkud Y, Fuhlbrigge RC, Rabinovich CE. Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry Investigators. Baseline description of the juvenile localized scleroderma subgroup from the childhood arthritis and rheumatology research alliance legacy registry. ACR Open Rheumatol. 2019;1(2):119-24. doi: 10.1002/acr2.1019
  18. Harrington CI, Dunsmore IR. An investigation into the incidence of auto-immune disorders in patients with localized morphoea. Br J Dermatol. 1989;120(5):645-8.
  19. Jacobe H, Ahn C, Arnett FC, Reveille JD. Major histocom- patibility complex class I and class II alleles may confer susceptibility to or protection against morphea: findings from the morphea in adults and children cohort. Arthritis Rheumatol. 2014;66(11):3170-7.
  20. Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nat Immunol. 2010;11(5):373-84.
  21. Kurzinski K, Torok KS. Cytokine profiles in localized scleroderma and relationship to clinical features. Cytokine. 2011;55(2):157-64. doi: 10.1016/j.cyto.2011.04.001

Supplementary files

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2. Fig. 1. Clinical forms of limited scleroderma and dermatoses similar to it. a - limited scleroderma in a patient of the 1st group: rashes are represented by erythematous spots with a purple tint, irregular in shape, in the center of the focus the color of the element is somewhat lighter than in the marginal area; b - annular granuloma in a patient of the 2nd group: the rash is represented by erythematous spots with a purple corolla along the periphery; c - small-plaque parapsoriasis in a patient of the 3rd group: the rash is represented by erythematous spots of various shapes, with clear boundaries, 5–10 cm in diameter; there is a more intense staining of the peripheral part of the lesions; d - large plaque parapsoriasis in a patient of the 4th group: rashes are represented by erythematous spots on the skin of the trunk and mammary glands.

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3. Fig. 2. The histological picture of patients with limited scleroderma (a) and annular granuloma (b). a - limited scleroderma: in the histological specimen the smoothness of the dermo-epidermal junction, homogenization of collagen fibers in the papillary dermis, diffuse and perivascular lymphohistiocytic infiltrate with an admixture of plasma cells in the reticular dermis are noted. Hematoxylin and eosin staining, x 200; b - annular granuloma: in the micrograph, histological changes in the reticular dermis are represented by thickened collagen fibers, scanty lymphohistiocytic infiltrate; there are no changes in the epidermis. Hematoxylin and eosin staining, x 400.

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4. Fig. 3. Immunohistochemical study in patients with limited scleroderma of I and II subgroups. 1a, 2a - a pronounced positive reaction in the dermis of patients of I and II subgroups. Immunohistochemical reaction using antibodies to CD4 + lymphocytes. Nuclear staining. 1a - x 40, 2a - x 100; 1b - a pronounced positive reaction in the dermis of patients of subgroup I; 2b - moderately pronounced positive reaction in the dermis of patients of subgroup II. Immunohistochemical reaction using antibodies to CD8 + lymphocytes. Nuclear and cytoplasmic staining. 1b, 2b - x 100; 1c - weak expression of vimentin in the dermis of patients of subgroup I; 2c - strong expression of vimentin in the dermis of patients of subgroup II. Immunohistochemical reaction using antibodies to vimentin. The staining is cytoplasmic. 1c, 2c - x 40; 1d - strong expression of IL-2 in the dermis of patients of subgroup I; 2d - weak expression of IL-2 in the dermis of patients of subgroup II. Immunohistochemical reaction using antibodies to IL-2. The staining is cytoplasmic. 1g, 2g - x100; 1e - weak expression of IL-4 in the dermis of patients of subgroup I; 2e - strong expression of IL-4 in the dermis of patients of subgroup II. Immunohistochemical reaction using antibodies to IL-4. The staining is cytoplasmic. 1e, 2e - x 40. 1f - strong expression of TLR7 in the dermis of patients of subgroup I; 2f - weak expression of TLR7 in the dermis of patients of subgroup II. Immunohistochemical reaction using antibodies to TLR7. Nuclear and cytoplasmic staining. 1e - x 40; 2e - x 100.

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5. Fig. 4. Pathogenesis of limited scleroderma.

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