Immunological Therapy in Persistent Complex Regional Pain Syndrome: A Systematic Review and Narrative Synthesis

Area of Science:

• Immunology
• Neurology
• Pain Management

Background:

• Complex Regional Pain Syndrome (CRPS) is thought to involve immunological mechanisms.
• Clinical observations and laboratory studies suggest abnormal immune activation in CRPS patients.
• This review focuses on therapies targeting the immune system for persistent CRPS.

Purpose of the Study:

• To systematically review the efficacy of immune-modulating therapies in adults with persistent CRPS (disease duration >1 year).

Main Methods:

• Searched major databases (PubMed, Embase, Scopus, etc.) up to April 2024 for CRPS and immune therapies.
• Screened titles, abstracts, and full texts; analyzed reference lists.
• Appraised randomized controlled trials using Cochrane Risk of Bias (RoB2).

Main Results:

• 1404 studies identified; 23 articles analyzed.
• Narrative synthesis used due to study heterogeneity.
• 16 reports suggested benefits from non-randomized studies; small RCTs showed possible benefits for some therapies (immunoglobulin, EGFR inhibitors, mycophenolate), but larger RCTs found no effect for immunoglobulin and lenalidomide.

Conclusions:

• Emerging immune therapies for persistent CRPS show promise.
• High-quality randomized trial evidence is limited and currently does not support positive treatment effects.
• Further high-quality clinical trials are needed to validate the efficacy of immunomodulating therapies in CRPS.