Immunologic underpinnings and treatment of morphea

ABSTRACT

Introduction

Morphea is a chronic autoimmune fibrosing condition of the skin and underlying tissue with the potential for significant disease-associated morbidity. While the exact etiology of morphea is not fully elucidated, many studies have explored the immunologic drivers of this disease.

Areas covered

Using PubMed, we performed a systematic review on morphea, with a focus on both the immune-mediated pathophysiology and treatment of this disease. Based on these findings, we review the literature surrounding what is understood about the role of the immune system in disease onset and course. Additionally, we discuss current treatments used in this disease as well as the potential role for more targeted therapies in the future.

Expert opinion

Much work remains to fully elucidate each step in the immunologic march causing morphea. However, there is evidence to suggest that the early inflammatory stages of morphea may be driven predominantly by immunologic events in the Th1/Th17 pathway, while the Th2 pathway may be responsible for the fibrosis and damage observed later in the disease. Standard of care treatments currently continue to focus on therapeutics with broad immune modulating properties. Further work exploring the immunologic underpinnings of morphea will facilitate more targeted treatment approaches over time.

KEYWORDS:

• Morphea
• localized scleroderma
• connective tissue disease
• autoimmune skin disease
• fibrosing disorder
• en coup de sabre

Article highlights

• Morphea is a chronic autoimmune fibrosing condition of the skin and underlying tissue with the potential for significant disease associated morbidity.

• The exact pathogenesis of morphea has yet to be fully elucidated.

• Early inflammatory phases of morphea are thought to be driven by the Th1/Th17 pathway.

• The Th2 pathway may be the primary driver behind disease fibrosis and damage.

• To date, broad immunomodulators are considered the mainstay of treatment for morphea.

• A better understanding of disease pathogenesis will allow for more targeted treatment approaches with time.

Declaration of interest

A LaChance is the PI for a research grant funded by Pfizer exploring the role of JAK/STAT in CTDs. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One peer reviewer has received research, speaking and/or consulting support from Eli Lilly and Company, GlaxoSmithKline/Stiefel, AbbVie, Janssen, Alovtech, vTv Therapeutics, Bristol-Myers Squibb, Samsung, Pfizer, Boehringer Ingelheim, Amgen Inc, Dermavant, Arcutis, Novartis, Novan, UCB, Helsinn, Sun Pharma, Almirall, Galderma, Leo Pharma, Mylan, Celgene, Valeant, Menlo, Merck & Co, Qurient Forte, Arena, Biocon, Accordant, Argenx, Sanofi, Regeneron, the National Biological Corporation, Caremark, Advance Medical, Suncare Research, Informa, UpToDate and the National Psoriasis Foundation. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.