Medically Unexplained Symptoms Are Linked to Chronic Inflammatory Diseases: Is There a Role for Frontal Cerebral Blood Oxygen Content?

Introduction: Patients often go to the physician with medically unexplained symptoms (MUS). MUS can be autonomic nervous system-related "unspecific" symptoms, such as palpitations, heart rhythm alterations, temperature dysregulation (hand, feet), anxiety, or depressive manifestations, fatigue, somnolence, nausea, hyperalgesia with varying pains and aches, dizziness, etc. Methods: In this real-world study, we investigated MUS in a cohort of unselected outpatients from general practitioners in Italy. It was our aim to increase the understanding of MUS by using principal component analyses to identify any subcategories of MUS and to check a role of chronic inflammatory diseases. Additionally, we studied cerebral blood oxygen (rCBO2) and associations with MUS and chronic inflammatory disease.

Results: Participants included 1,597 subjects (50.6 ± 0.4 years, 65%/35% women/men). According to ICD-10 codes, 137 subjects had chronic inflammatory diseases. MUS were checked by a questionnaire with a numeric rating scale and cerebral blood flow with optical techniques. The analyses of men and women were stratified. Psychological symptom severity was higher in the inflamed compared to the non-inflamed group (fatigue, insomnia in women and men; recent mood changes, daytime sleepiness, anxiety, apathy, cold hands only in women; abnormal appetite and heart rhythm problems only in men). Principal component analysis with MUS provided new subcategories: brain symptoms, gut symptoms, and unspecific symptoms. Brain and gut symptoms were higher in inflamed women and men. Chronic inflammatory diseases and pain were tightly interrelated in men and women (p < 0.0001). In women, not in men, average frontal rCBO2 content was higher in inflamed compared to non-inflamed subjects. In men, not in women, individuals with pain demonstrated a lower average frontal rCBO2 content compared to pain-free men. MUS did not relate to rCBO2 parameters.

Conclusion: This study shows close relationships between MUS and chronic inflammatory diseases but not between MUS and rCBO2 parameters.