Chronic fatigue syndrome is characterized by persistent fatigue and other specific symptoms that last for a minimum duration of six months.
Presentation
This syndrome presents with a sudden onset of flu-like symptoms with no prior history of severe exhaustion. With the onset of flu-like symptoms, the patient complains of severe exhaustion even after minimal physical exertion [8].
Along with severe fatigue, there may be other general symptoms like anorexia, nausea, and vomiting. There may be nightly drenching sweats.
Cognitive symptoms are very prominent and mainly include memory loss, poor concentration, and lack of alertness. Intelligence, language, and power of reasoning are not affected. Cognitive symptoms are very important for a diagnosis, without this the disorder cannot be concluded.
Mood fluctuations mainly anxiety, irritability, and depression will be seen.
There can be severe joint and muscular pains associated with other conditions like fibromyalgia, irritable bowel syndrome, and any sensitivity to foods, medications, and chemicals.
Though the symptom presentation will be more or less similar in most of the patients, the functional capacity varies. Some can lead fairly normal lives while others are bedridden. Due to severe physical and mental exhaustion, work and social activities are greatly reduced.
Entire Body System
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Fatigue
Assignment of Fatigue Groups We classified subjects into one of six fatigue categories, as outlined above (No Fatigue, Prolonged Fatigue, Chronic Fatigue, Explained Syndromic Fatigue, CFS-like, or CFS). [doi.org]
Evidence for sensitized fatigue pathways in patients with chronic fatigue syndrome. Pain. 2015;156:750. [mayoclinic.org]
Chronic fatigue syndrome is an illness characterized by disabling fatigue of at least 6 months, accompanied by several other symptoms. This review summarizes the current state of knowledge about chronic fatigue syndrome. [ncbi.nlm.nih.gov]
Abstract OBJECTIVE: Chronic fatigue syndrome is an illness characterized by disabling fatigue of at least 6 months, accompanied by several other symptoms. This review summarizes the current state of knowledge about chronic fatigue syndrome. [dx.doi.org]
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Chronic Fatigue Syndrome
Chronic fatigue syndrome is diagnosed on the basis of symptoms. Patients with chronic fatigue syndrome experience significant functional impairment. [ncbi.nlm.nih.gov]
Risk factors Factors that may increase your risk of chronic fatigue syndrome include: Age. Chronic fatigue syndrome can occur at any age, but it most commonly affects people in their 40s and 50s. Sex. [mayoclinic.org]
Neuropsychological deficits in patients with chronic fatigue syndrome. [doi.org]
RESULTS: Chronic fatigue syndrome is diagnosed on the basis of symptoms. Patients with chronic fatigue syndrome experience significant functional impairment. [dx.doi.org]
[…] treating both chronic fatigue syndrome and other symptoms. [ajp.psychiatryonline.org]
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Pain
Furthermore depression seemed not related to pain in CFS and a staphylococcus toxoid vaccine caused no significant pain reduction. [ncbi.nlm.nih.gov]
Fransen, Association Between Fatigue and Pain in Rheumatoid Arthritis: Does Pain Precede Fatigue or Does Fatigue Precede Pain?, Arthritis Care & Research, 65, 6, (862), (2013). [doi.org]
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Malaise
Also, an association with symptoms of post-exertional malaise was demonstrated. [ncbi.nlm.nih.gov]
Adults typically experience worsening post-exertional malaise (PEM), unrefreshing sleep, cognitive problems and/or orthostatic intolerance, in addition to any of the other symptoms in the list above. [health.ny.gov]
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Fever
The effect of antibiotic therapy on post-Q-fever fatigue syndrome has not been studied in south-east Europe thus far. Three patients are presented with post-Q-fever fatigue syndrome. All fulfilled the CDC criteria for chronic fatigue syndrome. [ncbi.nlm.nih.gov]
Syndrome thought to be caused by a viral organism resulting in chronic fatigue, fever, pain, sore throat, and, in some cases, depression ICD-9-CM Volume 2 Index entries containing back-references to 780.71 : [icd9data.com]
There exist two specific criteria that must be met for a diagnosis of CFS: (1) severe fatigue lasting six months or longer and (2) the coexistence of any four of a number of characteristic symptoms, defined as mild fever, sore throat, tender lymph nodes [britannica.com]
Respiratoric
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Pharyngitis
Physical findings are usually unspecific, and a large variety of signs can be found, such as pharyngeal soreness, fever, tender posterior cervical or axillary lymph nodes, muscular tenderness on palpation, and, occasionally, rash. [doi.org]
Examination of the patient's pharynx may show non-exudative pharyngitis (often referred to as "crimson crescents"). Cervical and axillary lymph nodes may be palpable and tender. [web.archive.org]
Gastrointestinal
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Abdominal Pain
Up to half of patients with CFS may experience symptoms including abdominal pain, alcohol intolerance, bloating, chest pain, chronic cough, diarrhea, dizziness, dry eyes or mouth, earaches, irregular heartbeat, jaw pain, morning stiffness, nausea, night [onhealth.com]
This orthostatic (upright) intolerance may manifest as increased fatigue, weakness, naurea, abdominal pain, poor concentration, nervousness, shortness of breath, lightheadedness, headache, tremulousness, palpitations, and even faintness. [cfidsselfhelp.org]
Abdominal pain is distressing [10], often requiring analgesia for relief. A previously unrecorded symptom in CFS patients is nocturnal diarrhoea, which disrupts an already disturbed sleep pattern. [bmcgastroenterol.biomedcentral.com]
This orthostatic (upright) intolerance may manifest as increased fatigue, weakness, nausea, abdominal pain, poor concentration, nervousness, shortness of breath, lightheadedness, headache, tremulousness, palpitations, and even faintness. [cfsselfhelp.org]
Examples include irritable bowel syndrome (IBS), functional dyspepsia, and functional abdominal pain syndrome. [publichealth.va.gov]
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Abdominal Cramps
Digestive disturbances – These include; nausea, loss of appetite, indigestion, excessive wind, bloating, abdominal cramps, alternating diarrhea and constipation. These symptoms are often similar to IBS. [hacw.nhs.uk]
Mild to moderate infection The most common signs and symptoms of mild to moderate C. difficile infection are: Watery diarrhea three or more times a day for two or more days Mild abdominal cramping and tenderness Severe infection People who have a severe [mayoclinic.org]
Patients with mild C. difficile colitis may have: a low-grade fever, mild diarrhea (5-10 watery stools a day), mild abdominal cramps and tenderness. [medicinenet.com]
You can have diarrhea and abdominal cramping even with a mild infection. If you have C. diff, your diarrhea will have a very strong odor. In more serious infections, there may be blood in the stool. [webmd.com]
In its mildest form, CDAD produces watery diarrhea at least three times a day, usually accompanied by lower abdominal cramps. Bleeding and fever are absent, and patients have a normal number of white blood cells. [health.harvard.edu]
Cardiovascular
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Chest Pain
Up to half of patients with CFS may experience symptoms including abdominal pain, alcohol intolerance, bloating, chest pain, chronic cough, diarrhea, dizziness, dry eyes or mouth, earaches, irregular heartbeat, jaw pain, morning stiffness, nausea, night [onhealth.com]
Cardiological or respiratory causes should be considered for shortness of breath and chest pain, and many other illnesses, depending on the specific symptoms. [patient.info]
Some people also report a range of other symptoms such as nausea, loss of appetite, irritable bowel syndrome, bloating, diarrhoea, irregular heartbeat, chest pain, jaw pain, night sweats, increased sensitivity to alcohol or medication, chronic cough, [healthnavigator.org.nz]
pains Jaw pain (possibly TMJ, as an overlapping condition) Flu-Like Symptoms You may feel like you are sick all of the time or symptoms may recur frequently. [verywellhealth.com]
Eyes
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Photophobia
[…] weight change, nausea, bowel disturbance) 53 Muscle and multiple joint pain 62 Cognitive problems 16 Sleep disturbance 27 Impairment of short term memory &/or concentration 28 Fatigue 85 Other clinical features: Visual changes, including blurring and photophobia [doi.org]
Case Presentation A 58-year-old patient presented to our outpatient clinic complaining of severe diffuse pain, insomnia, diarrhea, abdominal pain, bloating, photophobia, hyper- sensitivity to odor, noise, light touch, tinnitus and palpitations. [scirp.org]
Headaches were not associated with nausea, vomiting, or visual changes (eg, photophobia). Gastrointestinal issues such as diarrhea or constipation (n 52, 8%) were common, but these occurred without abdominal pain (0.2%), nausea, or vomiting (0.7%). [dovepress.com]
Musculoskeletal
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Arthralgia
Individuals with fibromyalgia (FM) and/or chronic fatigue syndrome (CFS) report arthralgias and myalgias. However, only persons with FM alone exhibit abnormal pain responses to mild levels of stimulation, or allodynia. [ncbi.nlm.nih.gov]
Epstein-Barr virus syndrome is a poorly defined symptom complex characterized primarily by chronic or recurrent debilitating fatigue and various combinations of other symptoms, including sore throat, lymph node pain and tenderness, headache, myalgia, and arthralgias [doi.org]
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Muscle Weakness
In all three groups, a majority of patients exhibited muscle weakness in the lower limbs, and significant numbers of patients had absent or abnormal reflexes. [ncbi.nlm.nih.gov]
Other symptoms include sore throat, fever, muscle weakness, headache, and joint pain A syndrome characterized by persistent or recurrent fatigue, diffuse musculoskeletal pain, sleep disturbances, and subjective cognitive impairment of 6 months duration [icd9data.com]
Other common symptoms include: Joint pain without swelling or redness, muscle aches, muscle weakness all over, or headaches that differ from those you have had in the past Sore throat, sore lymph nodes in the neck or under the arms, chills and night sweats [medlineplus.gov]
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Back Pain
Roussel, Jo Nijs, Mira Meeus, Veit Mylius, Cécile Fayt and Rob Oostendorp, Central Sensitization and Altered Central Pain Processing in Chronic Low Back Pain, The Clinical Journal of Pain, 29, 7, (625), (2013). S. A. A. van Dartel, J. W. J. [doi.org]
A 2001 study on chronic, non-specific low back pain (Keitel) provides some evidence that capsaicin cream can help people with this type of low back pain who also have fibromyalgia. [verywellhealth.com]
A literature search was performed through PubMed and Ovid using the terms fibromyalgia, temporomandibular joint disorder, irritable bowel syndrome, irritable bladder/interstitial cystitis, headache, chronic low back pain, chronic neck pain, functional [ncbi.nlm.nih.gov]
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Muscle Twitch
twitching Sleep disruptions Muscle and joint pains, and headaches Lowered blood pressure and feelings of dizziness and paleness Palpitations with an increased heart rate and shortness of breath Allergies Gastrointestinal changes, such as nausea, constipation [doctordoctor.com.au]
BFS has a variety of symptoms, including (but not limited to) frequent muscle twitches, muscle cramping, easy muscle fatigue, muscle aches and a "stiff" feeling, shakiness (tremors), and exercise intolerance. [web.archive.org]
Three patients reported that they had first-degree relatives with muscle cramps or muscle twitching but nothing to suggest ALS. [nextination.com]
Neurological symptoms: Problems with memory, concentration, cognition, word recognition Sensitivity to sound, light, smell, and touch Paraesthesiae, muscle twitching Sudden attacks of severe generalized pain ("Sensory Storms") Autonomic symptoms: Problems [doi.org]
General Symptoms Visual disturbances (blurring, light sensitivity, eye pain, worsening vision, dry eyes) Dry mouth and eyes (sicca syndrome) Rashes Unexplained weight changes Muscle twitching Seizures Recurrent infections Frequent canker sores Psychological [verywellhealth.com]
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Neck Pain
A literature search was performed through PubMed and Ovid using the terms fibromyalgia, temporomandibular joint disorder, irritable bowel syndrome, irritable bladder/interstitial cystitis, headache, chronic low back pain, chronic neck pain, functional [ncbi.nlm.nih.gov]
Soo Yun, You Lim Kim and Suk Min Lee, The effect of neurac training in patients with chronic neck pain, Journal of Physical Therapy Science, 27, 5, (1303), (2015). Lotte Bloot, Marianne J. [doi.org]
However, only half of women who have heart attacks have chest pain.Women are more likely than men to report back or neck pain, indigestion, heartburn, nausea, vomiting, extreme fatigue, or problems breathing (30). [docsopinion.com]
Patients also described chronic pain behind the eyes, neck pain, neuropathic or nerve pain, “full-body ice-cream-headache-like pains,” and feeling like “my brain was going to explode” (FDA, 2013, p. 14). [nap.edu]
Skin
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Night Sweats
Many people with chronic fatigue syndrome may experience other symptoms, including irritable bowel; depression or other psychological problems; chills and night sweats; visual disturbances; inability to think clearly; difficulty maintaining upright position [arthritis.org]
sweats, psychological problems (depression, irritability, anxiety, panic attacks), shortness of breath, skin sensations, tingling sensations, and weight loss. [onhealth.com]
Other common symptoms include: Joint pain without swelling or redness, muscle aches, muscle weakness all over, or headaches that differ from those you have had in the past Sore throat, sore lymph nodes in the neck or under the arms, chills and night sweats [medlineplus.gov]
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Flushing
"It appears that ME/CFS patients are flush with cytokines until around the three-year mark, at which point the immune system shows evidence of exhaustion and cytokine levels drop." This shows there are distinct stages to the disease, she said. [bbc.com]
“It appears that ME/CFS patients are flush with cytokines until around the three-year mark, at which point the immune system shows evidence of exhaustion and cytokine levels drop,” says Dr. Hornig. [mailman.columbia.edu]
[…] memory &/or concentration 28 Fatigue 85 Other clinical features: Visual changes, including blurring and photophobia 1 Emotional lability 23 Impaired temperature control, with intolerance of extremes of temperature 4 Vasomotor instability, with e.g. flushing [doi.org]
When handling capsaicin, be sure to: Wear gloves Don't expose the skin to heat, such as from a heating pad or when your skin is heated up from a shower or bath Keep away from eyes and flush eyes with water if it gets in them Don't use it on broken or [verywellhealth.com]
[…] home until at least 48 hours after your symptoms have cleared up wash your hands regularly with soap and water, particularly after going to the toilet and before eating – use liquid rather than bar soap clean contaminated surfaces (such as the toilet, flush [nhs.uk]
Psychiatrical
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Mood Swings
In addition to severe fatigue, symptoms include light sensitivity, headache, muscle and joint pain, difficulty concentrating, mood swings, and depression. Treatments may include medicines, exercise, supplements, and counseling. [massgeneral.org]
These include a lack of motivation, low energy, poor focus, poor memory, emotional mood swings, fatigue, muscle tension and more. [draxe.com]
swings Cardiovascular and Respiratory Symptoms A feeling of an irregular heartbeat Shortness of breath Frequent, hard to treat respiratory infections Common Overlapping Conditions Overlapping conditions are separate conditions that commonly occur in [verywellhealth.com]
Here are the typical symptoms: Foggy head Mood swings A ‘wired’, anxious feeling in the body Fatigue Aggravation from sugar Oral, vaginal or rectal thrush. [chronicfatiguesyndrome.net.au]
Neurologic
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Headache
Symptoms of cfs include fatigue for 6 months or more and experiencing other problems such as muscle pain, memory problems, headaches, pain in multiple joints, sleep problems, sore throat and tender lymph nodes. [icd9data.com]
Chronic fatigue syndrome (CFS) is a condition characterized by impairment of neurocognitive functions and quality of sleep and of somatic symptoms such as recurrent sore throat, muscle aches, arthralgias, headache, and postexertional malaise. [ncbi.nlm.nih.gov]
[…] be met for a diagnosis of CFS: (1) severe fatigue lasting six months or longer and (2) the coexistence of any four of a number of characteristic symptoms, defined as mild fever, sore throat, tender lymph nodes, muscle pain and weakness, joint pain, headache [britannica.com]
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Irritability
This review demonstrates that sympathetic nervous system predominance is common in fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, and interstitial cystitis. [ncbi.nlm.nih.gov]
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Sleep Disturbance
STUDY OBJECTIVES: Little is known about the type and severity of sleep disturbances in the pediatric chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) population, compared with healthy adolescents. [ncbi.nlm.nih.gov]
Given that sleep disturbance is a common symptom of psychiatric conditions, 31 it could be argued that sleep disturbance in CFS/ME is a secondary consequence of comorbid depression. [doi.org]
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Cognitive Impairment
The key neuropsychological problems reported by CFS patients are also included in the review in an effort to understand the significance of cognitive impairment in CFS. [ncbi.nlm.nih.gov]
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Confusion
CFS: (1) severe fatigue lasting six months or longer and (2) the coexistence of any four of a number of characteristic symptoms, defined as mild fever, sore throat, tender lymph nodes, muscle pain and weakness, joint pain, headache, sleep disorders, confusion [britannica.com]
[…] that subtyping individuals with CFS on sociodemographic, functional disability, viral, immune, neuroendocrine, neurology, autonomic, and genetic biomarkers can provide clarification for researchers and clinicians who encounter CFS' characteristically confusing [ncbi.nlm.nih.gov]
For centuries its confusing array of features has been attributed to numerous environmental, metabolic, infectious, immunologic, and psychiatric disturbances. [doi.org]
Workup
There is no single symptom or test to diagnose this condition. Diagnosis is mainly based on the exclusion of other medical conditions that can produce fatigue mainly AIDS, malignancy, and thyroid or adrenal conditions.
When a patient presents with fatigue after any physical activity as the main complaint, a thorough physical examination and blood examination must be done to exclude any other systemic disease.
For a clinical diagnosis there are certain essential criteria that should be present for an accurate diagnosis mainly:
- Short term memory loss/concentration difficulties
- Physical or mental exertion brings about severe malaise
- Altered and unrefreshing sleep
- Myalgia
- Arthralgia
- Sore throat which is persistent or recurring
- Tender lymph nodes mainly cervical and axillary
At least four of these criteria should be met along with dysfunctional cognitive symptoms.
Blood examination will show a low ESR, thus showing no signs of inflammation or infection. MRI and CT scans show no abnormality. Blood tests may be done to detect any antibodies if there was any prior infection.
Since mood-related symptoms are prominently seen, other mental health conditions like schizophrenia, depression, bipolar disorder need to be ruled out. A psychiatrist will be able to diagnose if any one of the above conditions is causing undue fatigue.
Treatment
As there is no known etiology for this condition there is no well-established mode of treatment. The treatment is mainly symptomatic. The objective is to improve the functional capacity of the patients so that they are able to carry out their daily activities with minimal fatigue.
The physician should plan the treatment according to the personal needs and status of the patient. This treatment should be modified from time to time depending on the medical condition and symptoms.
Prognosis
Recovery rates are good with proper treatment. Individuals are able to resume their daily activities. Relapses and remissions occur [6]. With treatment patients can recover within two years. Severe persistent cases show poor prognosis. Children and adolescents show better recovery rates. Regular monitoring is necessary as treatment requires modification according to status and symptoms of the condition [7].
Etiology
Chronic fatigue syndrome is supposed to have multiple factors responsible but the exact etiology still remains unknown. Several theories have been postulated but there is no documented evidence. Viruses have been implicated in the causation of chronic fatigue syndrome; the most common associated viruses are Epstein-Barr virus (EBV) and herpes simplex 6 virus. Other immunosuppressive conditions like AIDS, malignancy, and thyroid disorders also have a certain role to play. These conditions also produce symptoms similar to chronic fatigue syndrome. Any abnormality in the immune system can trigger off this condition.
Genetic predisposition and familial tendency seem to play a role in this disorder. Depression, emotional instability, and mental fatigue are seen in cases with the condition but there is an uncertainty whether it’s a result or causation.
Recent studies show any period of stress, trauma, or emergency situations cause the hypothalamic-pituitary-adrenal axis (HPA) to fluctuate resulting in abnormal hormonal response causing a decreased production of cortisol [3]. There is no single causative agent, but the interplay of all the above factors produces this syndrome.
Epidemiology
Since there are various definitions for the condition, the exact prevalence also varies. The condition affects all races and ethnic backgrounds. There is a female preponderance usually affecting women between 30-50 years of age. Children and young adults are rarely affected [4]. It is not a contagious disease but shows a familial tendency.
Pathophysiology
The pathogenesis still remains unknown in spite of many years of research. Many theories have been postulated, but no single theory has been pointed out in the etiopathogenesis.
On the basis of the clinical presentation, etiopathogenesis has been documented. Other investigations demonstrated abnormalities in other aspects including human brain functioning, immune responses, neuroendocrine responses and psychological tendencies [5]. Genetic predisposition is also considered vital for the manifestation of chronic fatigue syndrome.
Several investigations reveal the role of central nervous system due to several symptoms including difficulty in concentration, memory loss and lack of alertness. Various imaging techniques like MRI show significant changes in the subcortical white matter of the affected individuals. Other tests show decreased cerebral blood flow.
Imbalance in hypothalamic-pituitary-adrenal axis is also implicated including serotonin pathways. Abnormal response to stress or trauma is considered as a reason. Many patients also show decreased cortisol.
Viral infections like EBV virus or Herpes 6 virus have been implicated as patient’s blood shows antibodies to these infections. So post viral infection, patients present with chronic fatigue. Immune system also seems to play a role in the etiology, mainly immunocompromised states.
However, the outcome and medical utility of these findings still remains elusive. Chronic fatigue syndrome is a complex syndrome with varied pathophysiological abnormalities manifesting similar signs.
Due to a wide spectrum of symptoms and a number of physiological, pathological and psychological pathways playing a role, it makes the pathogenesis multifactorial.
Prevention
There is no known prevention for chronic fatigue syndrome as the exact cause is not known.
Once diagnosed, prevention of aggravation of symptoms includes avoiding stimulants, stress and too much sleep. These factors are known to trigger the symptoms. Too much overexertion should be avoided.
Summary
Chronic fatigue syndrome is a state of of persistent fatigue that remains without any explanation for a minimum duration of 6 months. The cardinal symptoms are fatigue, memory loss, poor concentration, irritability, altered sleep patterns and muscle aches [1].
This syndrome was earlier known as myalgic encephalomyelitis (ME) and has been attributed to a viral infection. There is however no documented evidence of any infective cause of this condition at present. Laboratory investigations are normal.
The syndrome usually disables the individual to perform daily activities due to profuse exhaustion, lack of concentration and memory loss. This leads to depression in the patients. Genetic and psychological mechanisms also seem to play a role in this condition. The severity of symptoms varies from individual to individual.
The proportion of patients with organic disease remains uncertain [2]. Recent studies suggest that two thirds of patients with symptom duration of more than 6 months have an underlying psychiatric disorder.
Patient Information
Chronic fatigue syndrome is a condition that causes severe fatigue. This fatigue persists even after periods of rest. Any physical or mental exertion brings about exhaustion, which restricts the individual from doing their daily activities. There is no known cause for this condition. Viral infections are thought to cause this condition.
This syndrome mainly shows fatigue which should be present for a minimum of 6 months to confirm this medical condition. Along with this, the patient will show memory loss, problems in sleeping, muscle and joint pains, and sore throat. These symptoms are important to confirm chronic fatigue syndrome.
This syndrome mainly affects women, and usually occurs between 30- 50 years of age. There are no specific tests for this condition and thus hard to detect by the physician. The exclusion of other medical conditions helps in the diagnosis.
Since the cause remains unknown, there is no specific treatment. Treatment is mainly directed towards relieving the symptoms shown by the patient. The aim of the treatment is to enable the individual to carry out daily activities and prevent from being totally bedridden. There is no total cure for this condition; periods of relapse and remission are common.
Regular monitoring and follow-up are important as the treatment will also be modified according to the condition of the patient. Total recovery is not possible, but lifestyle modifications and exercise therapy can help the patient lead a fairly normal life.
References
- Fukuda K, Straus SE, Hickie I, et al. The chronic fatigue syndrome: a comprehensive approach to its definition and study. International Chronic Fatigue Syndrome Study Group. Ann Intern Med. 1994 Dec 15; 121(12): 953-59.
- Sharpe M, Archard LC, Banatvala JE et al. A report: chronic fatigue syndrome: guidelines for research. J R Soc Med. 1991 Feb; 84(2): 118-21.
- Afari N, Buchwald D. Chronic fatigue syndrome: a review. Am J Psychiatry. 2003 Feb; 160(2): 221-36.
- Wessely S. The epidemiology of chronic fatigue syndrome. Epidemiol Rev. 1995; 17(1): 139-51.
- Harvey SB, Wadsworth M, Wessely S, et al. The relationship between prior psychiatric disorder and chronic fatigue: evidence from a national birth cohort study. Psychol Med. 2008 Jul; 38(7): 933-940.
- Joyce J, Hotopf M, Wessely S. The prognosis of chronic fatigue and chronic fatigue syndrome: a systematic review. QJM. 1997 Mar; 90(3): 223-33.
- Cairns R, Hotopf M. A systematic review describing the prognosis of chronic fatigue syndrome. Occup Med (Lond). 2005 Jan; 55(1): 20-31.
- Swanink CM, Vercoulen JH, Bleijenberg G, et al. Chronic fatigue syndrome: a clinical and laboratory study with a well matched control group. J Intern Med. 1995 May; 237(5): 499-506.