Comparing Efficacy of Intravenous vs. Subcutaneous Immunoglobulin Therapy for Chronic Fatigue Syndrome: A Scoping Review

Background and/or Objectives: Chronic Fatigue Syndrome (CFS), also known as myalgic encephalomyelitis (ME), is characterized by continual fatigue, bodily pain, cognitive dysfunction, and sleep disturbances. Limited treatments include immunoglobulin therapy, administered either via intravenous (IVIG) or subcutaneous (SCIG) routes, have been examined as potential intervention. However, comparative effectiveness, safety, and patient tolerability remain indeterminate. The purpose of this study is to systematically assess the available literature to evaluate the relative benefits and limitations of IVIG vs. SCIG in CFS management.

Design: A scoping review using the PRISMA-Scoping Review guidelines.

Setting : The literature was systematically searched across PubMed, Embase, Cochrane, and Scopus databases.

Participants : The inclusion criteria featured several studies within the last 10 years that evaluated IVIG and SCIG in CFS patients, clinical trials and their outcomes, improvement of symptoms and safety profiles. Articles not focusing on CFS/ME, those lacking comparative data, and non-human trials were excluded. Rayyan was used to screen articles for bias assessment and data extraction. Disagreements among the reviewers were resolved as a group.

Interventions: Comparison of IVIG vs. SCIG assessing efficacy, symptom relief, safety, and adherence.

Main Outcome Measures: Primary: Symptom improvement, functional outcomes, adverse effects.
Secondary: Patient adherence, cost-effectiveness, quality of life.

Results: Prior data suggest IVIG may alleviate symptoms in select CFS patients, especially those with immune dysfunction markers. Some studies demonstrated significantly improved fatigue, while others showed limited efficacy. SCIG appears better tolerated with less systemic side effects and improved adherence, though its effectiveness is less conclusive than IVIG. The limited large-scale comparative studies highlight the need for additional trials to determine optimal patient selection.

Conclusions: This analysis pinpoints key differences between IVIG and SCIG in CFS treatment, suggesting IVIG may benefit certain patients, while SCIG offers improved safety and adherence. Larger controlled trials are necessary to establish definitive guidelines and optimize personalized treatment strategies for CFS patients.