IOM Criteria Diagnosis requires that the patient have the following 3 symptoms: 1. Fatigue - substantial reduction or impairment in the ability to engage in pre illness levels of occupational, educational, social, or personal activities that persists for more than 6 months and is accompanied by fatigue, which is often profound, is of new or definite onset (not lifelong), is not the result of ongoing excessive exertion, and is not substantially alleviated by rest 2. Postexertional malaise (an exacerbation of some or all of an individual’s ME/CFS symptoms after physical or cognitive exertion, or orthostatic stress that leads to a reduction in functional ability), 3. Unrefreshing sleep - Feeling unrefreshed despite sleeping many hours and other sleep disturbances. At least 1 of the 2 following manifestations is also required: 1. Cognitive impairment OR 2. Orthostatic intolerance Notes: Frequency and severity of symptoms should be assessed. The diagnosis of systemic exertion intolerance disease (myalgic encephalomyelitis/chronic fatigue syndrome) should be questioned if patients do not have these symptoms at least half of the time with moderate, substantial, or severe intensity. Other clinical features that may be seen in patients with this disorder are a history of certain infections known to act as triggers for ME/CFS that preceded the onset of symptoms and many types of pain, including headaches, arthralgia, and myalgia. Other complaints, such as gastrointestinal and genitourinary problems, sore throat, tender axillary/cervical lymph nodes, and sensitivity to external stimuli, are reported less frequently (Buchwald and Garrity, 1994; Jason et al., 2013; McGregor et al., 1996). These features, when present, can support the diagnosis of ME/CFS. No exclusions required. Conclusion: One of the committee’s most important conclusions is that a thorough history, physical examination, and targeted workup are necessary and often sufficient for diagnosis of ME/CFS. ------------------------------------------------------------------------------------------------------------------------------------------ CCC Criteria 1. Fatigue: The patient must have a significant degree of new onset, unexplained, persistent, or recurrent physical and mental fatigue that substantially reduces activity level. 2. Post-Exertional Malaise and/or Fatigue: There is an inappropriate loss of physical and mental stamina, rapid muscular and cognitive fatigability, post exertional malaise and/or fatigue and/or pain and a tendency for other associated symptoms within the patient’s cluster of symptoms to worsen. There is a pathologically slow recovery period - usually 24 hours or longer 3. Sleep Dysfunction:* There is unrefreshed sleep or sleep quantity or rhythm disturbances such as reversed or chaotic diurnal sleep rhythms. 4. Pain:* There is a significant degree of myalgia. Pain can be experienced in the muscles, and/or joints, and is often widespread and migratory in nature. Often there are significant headaches of new type, pattern or severity. 5. Neurological/Cognitive Manifestations: Two or more of the following difficulties should be present: confusion, impairment of concentration and short-term memory consolidation, disorientation, difficulty with information processing, categorizing and word retrieval, and perceptual and sensory disturbances – e.g. spatial instability and disorientation and inability to focus vision. Ataxia, muscle weakness and fasciculations are common. There may be overload1 phenomena: cognitive, sensory – e.g. photophobia and hypersensitivity to noise - and/or emotional overload, which may lead to “crash”2 periods and/or anxiety. 6. At Least One Symptom from Two of the Following Categories: __ a. Autonomic Manifestations: orthostatic intolerance - neurally mediated hypotension (NMH), postural orthostatic tachycardia syndrome (POTS), delayed postural hypotension; light-headedness; extreme pallor; nausea and irritable bowel syndrome; urinary frequency and bladder dysfunction; palpitations with or without cardiac arrhythmias; exertional dyspnea. __ b. Neuroendocrine Manifestations: loss of thermostatic stability – subnormal body temperature and marked diurnal fluctuation, sweating episodes, recurrent feelings of feverishness and cold extremities; intolerance of extremes of heat and cold; marked weight change - anorexia or abnormal appetite; loss of adaptability and worsening of symptoms with stress. __ c. Immune Manifestations: tender lymph nodes, recurrent sore throat, recurrent flulike symptoms, general malaise, new sensitivities to food, medications and/or chemicals Notes: *There is a small number of patients who have no pain or sleep dysfunction, but no other diagnosis fits except ME/CFS. A diagnosis of ME/CFS can be entertained when this group has an infectious illness type onset. **Some patients have been unhealthy for other reasons prior to the onset of ME/ CFS and lack detectable triggers at onset or have more gradual or insidious onset. Exclusions: Exclude active disease processes that explain most of the major symptoms of fatigue, sleep disturbance, pain, and cognitive dysfunction. It is essential to exclude certain diseases, which would be tragic to miss: Addison’s disease, Cushing’s Syndrome, hypothyroidism, hyperthyroidism, iron deficiency, other treatable forms of anemia, iron overload syndrome, diabetes mellitus, and cancer. It is also essential to exclude treatable sleep disorders such as upper airway resistance syndrome and obstructive or central sleep apnea; rheumatological disorders such as rheumatoid arthritis, lupus, polymyositis and polymyalgia rheumatica; immune disorders such as AIDS; neurological disorders such as multiple sclerosis (MS), Parkinsonism, myasthenia gravis and B12 deficiency; infectious diseases such as tuberculosis, chronic hepatitis, Lyme disease, etc.; primary psychiatric disorders and substance abuse. Exclusion of other diagnoses, which cannot be reasonably excluded by the patient’s history and physical examination, is achieved by laboratory testing and imaging. If a potentially confounding medical condition is under control, then the diagnosis of ME/CFS can be entertained if patients meet the criteria otherwise.