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SummaryChronic fatigue syndrome (CFS) is a heterogeneous disorder of unknown aetiology characterized by disabling fatigue, headaches, sleep disturbance and several other symptoms. The onset of CFS may follow a viral infection or period of stress. Patients with CFS do not have hypogammaglobulinaemia, predisposition to recurrent bacterial infections or symptoms of autoimmunity. To date, defects in B cell numbers or function have not been shown in the literature. However, treatment with anti-B cell therapy using Rituximab has recently shown benefit to CFS patients. We therefore postulated that patients with CFS had a subtle humoral immune dysfunction, and performed extended B cell immunophenotyping. We undertook a detailed characterization of the proportions of the different B cell subsets in 33 patients with CFS fulfilling the Canadian and Fukada criteria for CFS and compared these with 24 age-and gender-matched healthy controls (HC). CFS patients had greater numbers of naive B cells as a percentage of lymphocytes: 6·3 versus 3·9% in HC (P = 0·034), greater numbers of naive B cells as a percentage of B cells: 65 versus 47% in controls (P = 0·003), greater numbers of transitional B cells: 1·8 versus 0·8% in controls (P = 0·025) and reduced numbers of plasmablasts: 0·5 versus 0·9% in controls (P = 0·013). While the cause of these changes is unclear, we speculate whether they may suggest a subtle tendency to autoimmunity.

ObjectiveTo assess five physical signs to see whether they can assist in the screening of patients with chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) and potentially lead to quicker treatment.MethodsThis was a diagnostic accuracy study with inter-rater agreement assessment. Participants recruited from two National Health Service hospitals, local CFS/ME support groups and the community were examined by three practitioners on the same day in a randomised order. Two allied health professionals (AHPs) performed independent examinations of physical signs including: postural/mechanical disturbances of the thoracic spine, breast varicosities, tender Perrin’s point, tender coeliac plexus and dampened cranial flow. A physician conducted a standard clinical neurological and rheumatological assessment while looking for patterns of illness behaviour. Each examination lasted approximately 20 min.ResultsNinety-four participants were assessed, 52 patients with CFS/ME and 42 non-CFS/ME controls, aged 18–60. Cohen’s kappa revealed that agreement between the AHPs was substantial for presence of the tender coeliac plexus (κ=0.65, p<0.001) and moderate for postural/mechanical disturbance of the thoracic spine (κ=0.57, p<0.001) and Perrin’s point (κ=0.56, p<0.001). A McNemar’s test found no statistically significant bias in the diagnosis by the experienced AHP relative to actual diagnosis (p=1.0) and a marginally non-significant bias by the newly trained AHP (p=0.052). There was, however, a significant bias in the diagnosis made by the physician relative to actual diagnosis (p<0.001), indicating poor diagnostic utility of the clinical neurological and rheumatological assessment.ConclusionsUsing the physical signs appears to improve the accuracy of identifying people with CFS/ME and shows agreement with current diagnostic techniques. However, the present study concludes that only two of these may be needed. Examining for physical signs is both quick and simple for the AHP and may be used as an efficient screening tool for CFS/ME. This is a small single-centre study, and therefore, further validation in other centres and larger populations is needed.

Several hypotheses have been proposed to explain the disabling fatigue with normal routine tests of inflammation, endocrinopathy and organ dysfunction that characterises chronic fatigue syndrome (CFS). It is quite possible that it represents the phenotypic endpoint of one or more pathogenic agents possibly acting on a background of stress, mood disturbance and disordered sleep to produce impaired immune function. Conflicting and inconsistent early reports regarding cytokine abnormalities and disturbance of CD4 and CD8 T cells has now given way to a new appreciation of the subtleties of the immune impairment in this condition. Thus impaired T cell homing and altered NK cell function combined with dysregulated B cell maturation are likely. The clinical benefits of anti-B cell monoclonal antibody therapy in particular has encouraged a more detailed analysis of these cells in CFS as it has in many systemic connective disorders. The notion of inefficient elimination of autoreactive B cells leading to a non-inflammatory quiet autoimmunity affecting the central nervous system and the immune system itself is proposed. This may explain the diverse range of symptoms evident in this enigmatic condition and even the incoherent immune reports that have hindered its understanding.