New aspects of localized scleroderma pathogenesis: practical basis

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.

Keywords

localized scleroderma / Morphea / immunopathgenesis / immunohistochemical assay

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