Chronic Fatigue Syndrome

Objective: The development of a score for severity of Chronic Fatigue Syndrome (CFS), the correlation of CFS with parameters of immune activation and the association with pathogens. Methods: Five hundred five patients with suspicion of Chronic Fatigue Syndrome and no other definitive diagnosis were checked by a 45-criteria-score, basic laboratory programs and immunological profiles. In most of the patients further tests concerning complement system, immune activation markers, hormones and serology of herpesviruses, Chlamydia and Borrelia could be evaluated. Comparison of the symptoms of CFS patients with healthy controls lead to a 30-criteria-score and this score was correlated with laboratory parameters (Spearman rank-correlation-coefficient rs, ties corrected). Results: Three hundred eighty-five patients fulfilling stronger criteria according to the Centers for Disease Control (CDC) definition showed significant differences to 53 healthy controls in 40 of the 45 criteria (p < 0.001, twitches and food allergies p < 0.05). Thirteen symptoms corresponding to CDC criteria were all significant (p < 0.001), 17 further significant criteria of descending precision were added: respiratory infections, palpitations, dizziness, dyspepsia, dryness of mouth/eyes, allergies, nausea, paresthesia, loss of hair, skin alterations, dyscoordination, chest pain, personality changes, eczema, general infections, twitches, urogenital infections. A correlation between the 30-criteria-score and immunological parameters could be evaluated in 472 of the 505 patients. Significant positive correlation with the 30-criteria-score was found in numbers of CD8+ T-lymphocytes, HLA-DR+ T-lymphocytes, gamma globulins, IgM, IgG, and for the number of types of autoantibodies (mainly ANA, ACA, antithyroid and antiparietal cell antibodies). Significant negative correlation was found in albumin-globulin-ratio, eosinophils and IgE. Most of these parameters also correlated with one another. On the other hand, in subgroups of the 505 patients the Frequency of positivity in serological tests for HHV-6 (49.9%), EBV (35.4%), HSV (29.2%), CMV (12.5%) and Chlamydia (35.0%) was striking. Borrelia Western blots showed 3 or more specific IgG-bands in 54 of 131 patients (41.2%). In some cases infection with EBV, HHV-6 and CMV, respectively, was confmed by DNA-PCR-test and antigen detection. Summary: In increasingly larger groups of patients with CFS and related constellations we often see clinical signs and longer anamnesis of other symptoms besides the classical criteria of CFS, especially a high prevalence of local and general susceptibility to infections and hints to prolonged inflammation processes. Together with other results, the data confirm the hypothesis that a reduced or unstable immune control or delayed immune reaction to persisting viruses or bacterial intracellular pathogens, possibly triggered by common infections or other environmental factors, can lead to a chronic neuroimmune activation state and auto-immune disorders. Hypersensitivity symptoms of the patients might not be mediated by classical allergies alone but also result from a type-lV-hypersensitivity.