Chronic fatigue syndrome differential diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Disease associations

Some diseases show a considerable overlap with CFS. According to an article in American Family Physician in 2002, Multiple Sclerosis, Thyroid disorders, anemia, and diabetes are but a few of the diseases that must be ruled out if the patient presents with appropriate symptoms.

People with fibromyalgia (FM, or Fibromyalgia Syndrome, FMS) have muscle pain and sleep disturbances. Fatigue and muscle pain occurs frequently in the initial phase of various hereditary muscle disorders and in several autoimmune, endocrine and metabolic syndromes; and are frequently labelled as CFS or fibromyalgia in the absence of obvious biochemical/metabolic abnormalities and neurological symptoms. Those with multiple chemical sensitivity (MCS) are sensitive to chemicals and have sleep disturbances. Many veterans with Gulf War syndrome (GWS) have symptoms almost identical to CFS. One study found several parallels when relating the symptoms of Post-polio syndrome with CFS, and postulates a possible common pathophysiology for the illnesses.

Although post-Lyme syndrome and CFS share many features/symptoms, a study found that patients of the former experience more cognitive impairment and the patients of the latter experience more flu-like symptoms.

One review (2006) found that there was a lack of literature to establish the discriminant validity of undifferentiated somatoform disorder from CFS. The author stated that there is a need for proponents of chronic fatigue syndrome to distinguish it from undifferentiated somatoform disorder. The author also mentioned that the experience of fatigue as exclusively physical and not mental is captured by the definition of somatoform disorder but not CFS. Hysterical diagnoses are not merely diagnoses of exclusion but require criteria to be met on the positive grounds of both primary and secondary gain. Primary Depression can be excluded in the differential diagnosis due to the absence of anhedonia and la belle indifference, the variability (lability) of mood, and the presence of sensory phenomena and somatic signs such as ataxia, myclonus and most importantly, exercise intolerance with paresis, malaise and general deterioration, which can in some cases become a comorbid situational depression.

Disease	Differentiating signs and symptoms	Diagnostic findings
Fibromyalgia	Symptoms have been present at a similar level for at least 3 months. Chronic musculoskeletal pain with multiple tender points Stiffness, numbness, and fatigue Headaches Sleep disorder	All lab tests are normal
Rheumatoid arthritis	Multiple joint swelling Morning stiffness Rheumatoid nodules	RF or anti-cyclic citrullinated protein (CCP) antibody is positive. Markers of systemic inflammation (ESR, CRP) are typically elevated.
SLE	Maculopapular rash Multi-system involvement	Positive anti-Smith antibodies
Chronic fatigue syndrome	Fatigue plus 4 of the following symptoms: Short-term memory loss Sore throat Tender lymph nodes in the neck or armpit Muscle pain Joint pain without swelling or redness Headaches Insomnia Malaise	Diagnosis of exclusions Symptoms must present for more than 6 months
Spondyloarthritis	Axial skeletal pain and stiffness Restricted spinal motion	Elevated ESR or CRP Negative RF Bamboo spine on x-ray
Polymyalgia rheumatica	Older at onset Generalized stiffness	An elevated erythrocyte sedimentation rate (ESR) OR C-reactive protein (CRP) Response to corticosteroids
Osteoarthritis	Localized joint pain Restricted to affect joints Older at onset	X-ray of the involved joints demonstrate degenerative changes
Hypothyroidism	Systemic symptoms such as weight gain, constipation, dry skin Muscular aching and prominent fatigue that improves on replacement of thyroid hormone.	TSH is elevated and free T4 is low.
Myopathaies (polymyositis and dermatomyositis)	Pelvic and shoulder girdle muscle weakness Rash	Muscle biopsy confirms the diagnosis Elevated CPK enzyme
Neuropathy	Numbness and tingling Paresthesia	Abnormal EMG