Comparative Nosology: ME/CFS Among Contested Diagnoses

NoteChapter Abstract

Systematic comparison of ME/CFS with fibromyalgia, irritable bowel syndrome, post-treatment Lyme disease, complex regional pain syndrome, Gulf War illness, mast cell activation syndrome, Ehlers-Danlos/hypermobility, Long COVID, and other post-infectious fatigue syndromes — examining diagnostic boundary disputes, shared mechanisms, treatment overlap, and the historical “splitting vs. lumping” debate.

NoteChapter Roadmap: How to Use This Chapter

For patients: read the splitting-vs-lumping and post-infectious sections to understand where ME/CFS sits among overlapping diagnoses, and the fibromyalgia/IBS overlaps if relevant to you.

For caregivers: read the splitting-vs-lumping section to understand why overlapping conditions complicate diagnosis and care. The comparative detail can be skimmed.

For clinicians: read the PTLDS and MCAS sections for boundary management and the overdiagnosis/underdiagnosis hazards, plus the POTS section on diagnostic validity.

For researchers: read the Long COVID, PTLDS, and GWI hypotheses and the shared-genetic-architecture speculations — they define testable splitting-vs-lumping predictions.

1 Contents

• The Splitting vs. Lumping Problem
• The Post-Infectious Syndrome Paradigm
• The Fibromyalgia Overlap
• The Connective Tissue Axis: Ehlers-Danlos, Hypermobility, and Craniocervical Instability
• The Mast Cell Axis: MCAS as Comorbidity vs. Comparator
• The Autonomic Spectrum: POTS and Dysautonomia
• The Autoimmune Model: CRPS as Existence Proof
• Gulf War Illness: The Multi-Hit Model
• The Gut-Brain Axis: IBS as Comorbidity and Comparator
• The Psychiatric and Psychosocial Overlap
• Diagnostic Boundary Disputes: Historical Lessons
• Research Directions
• Synthesis: A Framework for Comparative Nosology