Sclerosing skin disorders in association with multiple sclerosis. Coincidence, underlying autoimmune pathology or interferon induced?

Abstract

Sclerosing skin disorders may develop in the course of MS. The relatively early age of SSc onset in patients with MS suggests a genetic predisposition and/or an IFN-associated trigger.

Association between the IRF5 rs2004640 functional polymorphism and systemic sclerosis: A new perspective for pulmonary fibrosis

“…IFN regulatory factors, such as IFN regulatory factor 5, coordinate the expression of type I IFNs, which are suspected to play a pivotal role in the pathophysiology of connective tissue disorders such as SLE, SS, and SSc (3, 4, 6). Following the multiple reported observations of an acute SSc‐like phenotype in patients receiving IFNα or IFNβ therapy (for review, see ref 820), we sought to determine whether IRF5 rs2004640 could influence the fibrotic phenotype of SSc.…”

“…A recent investigation of immunologic alterations occurring in early systemic sclerosis (SSc), using transcriptional profiling of peripheral blood cells, demonstrated some parallels with the lupus IFN gene signature (6). A key role of IFN in autoimmunity is further supported by the well‐known induction by IFN therapy of various autoimmune diseases, such as thyroiditis, hepatitis, pernicious anemia, rheumatoid arthritis (7), and, even more recently, SSc (8, 9).…”

Update on the role of plasmacytoid dendritic cells in inflammatory/autoimmune skin diseases

“…Type 1 IFNs have also been implicated in the pathogenesis of localized cutaneous scleroderma (morphea) and systemic sclerosis (SSc). This was initially based on several clinical observations: IFN‐ β treatment has been reported to induce SSc‐like cutaneous sclerosis and TNF‐ α inhibitors, as secondary inducers of IFN‐ α production , have also been reported to cause localized skin thickening . Using microarray analysis of peripheral blood monocytes, one study has shown that patients with SSc have increased expression of a cluster of type 1 IFN‐regulated genes .…”

A potential contribution of antimicrobial peptide LL-37 to tissue fibrosis and vasculopathy in systemic sclerosis

“…For instance, in a clinical trial, withdrawal from the protocol occurred more frequently in patients with SSc treated with IFN‐α than in those treated with placebo, and most patients who dropped out of IFN‐α treatment experienced exacerbation of ILD . Furthermore, IFN‐α induces the onset of typical SSc or SSc‐like symptoms in genetically predisposed individuals . In SSc lesional skin, pDCs are distributed predominantly in the perivascular regions and highly express IFN‐α .…”