All ethnic groups and income levels are susceptible to the illness. The CDC states that CFS is "at least as common" in African Americans and Hispanics as Caucasians. A 2009 meta-analysis, however, showed that compared with the White American majority, African Americans and Native Americans have a higher risk of CFS, though it acknowledged that studies and data were limited. More women than men get CFS — between 60 and 85% of cases are women; however, there is some indication that the prevalence among men is underreported. The illness is reported to occur more frequently in persons between the ages of 40 and 59. CFS is less prevalent among children and adolescents than among adults.

Blood relatives of those who have CFS appear to be more predisposed. There is no direct evidence that CFS is contagious.

Psychological stress, childhood trauma, perfectionist personalities, old age, lower middle education, low physical fitness, preexisting psychological illness, and allergies may be risk factors for developing chronic fatigue syndrome. This has led some to believe that stress-related visceral responses underlie CFS. Pre-existing depressive and anxiety disorders, as well as high expectation of parents and family history were predisposing factors identified in another review.

People with CFS and their relatives tend to attribute their illness to physical causes (such as a virus or pollution) rather than to psychological causes. Such attributions are associated with increased symptoms and impairment, and worse outcomes over time.

The cause of CFS is unknown. Genetic, physiological and psychological factors are thought to work together to precipitate and perpetuate the condition. A 2016 report by the Institute of Medicine states that CFS is a biologically-based illness, but that the biologic abnormalities are not sensitive enough to be useful diagnosis.

It may begin as a flu-like illness with a sudden onset, or it may occur gradually. Because of this, various infectious causes have been proposed; however, there is insufficient evidence to support such causation. Infections proposed include mononucleosis, chlamydia, HHV-6, and lyme disease. Inflammation may be involved.

The most common causes of myalgia by injury are: sprains and strains.

Sudden cessation of high-dose corticosteroids, opioids, barbiturates, benzodiazepines, caffeine or alcohol can induce myalgia in many respects.

The average age at onset is 3–7 years, but CVS has been seen in infants who are as young as 6 days and in adults who are as old as 73 years. Typical delay in diagnosis from onset of symptoms is 2.7 – 3 years. Females show a slight predominance over males; the female-to-male ratio is 57:43.

How common the condition is, is not clear. A prospective study found that 3 in 100,000 five-year-olds are diagnosed with the condition. Two published studies on childhood CVS suggest nearly 2% of school-age children may have CVS. However, diagnosis is problematic and, as knowledge of CVS has increased in recent years, more and more cases are emerging.

Fitzpatrick et al. (2007) identified 41 children with CVS. The mean age of the sample was 6 years at the onset of the syndrome, 8 years at first diagnosis, and 13 years at follow-up. As many as 39% of the children had resolution of symptoms immediately or within weeks of the diagnosis. Vomiting had resolved at the time of follow-up in 61% of the sample. Many children, including those in the remitted group, continued to have somatic symptoms such as headaches (in 42%) and abdominal pain (in 37%).

Most children who have this disorder miss on average 24 school days a year. The frequency of episodes is higher for some people during times of excitement. Charitable organizations to support sufferers and their families and to promote knowledge of CVS exist in several countries.

The condition may be a sign of various disease states, including but not exclusive to the following:

- Cancers

- Lymphoma

- Leukemia

- Infections

- HIV/AIDS

- Tuberculosis

- Mycobacterium avium-intracellulare infection

- Infectious mononucleosis

- Fungal infections (histoplasmosis, coccidioidomycosis)

- Lung abscess

- Infective endocarditis

- Brucellosis

- Pneumocystis pneumonia (most often - in immunocompromised individuals)

- Endocrine disorders

- Menopause

- Premature ovarian failure

- Hyperthyroidism

- Diabetes mellitus (nocturnal hypoglycemia)

- Endocrine tumors (pheochromocytoma, carcinoid)

- Orchiectomy

- Rheumatic disorders

- Takayasu's arteritis

- Temporal arteritis

- Other

- Obstructive sleep apnea

- Gastroesophageal reflux disease

- Chronic fatigue syndrome

- Fibromyalgia

- Granulomatous disease

- Chronic eosinophilic pneumonia

- Lymphoid hyperplasia

- Diabetes insipidus

- Prinzmetal's angina

- Anxiety

- Pregnancy

- Drugs

- Antipyretics (salicylates, acetaminophen)

- Antihypertensives

- Dinitrophenol - a common side effect

- Phenothiazines

- Drug withdrawal: ethanol, benzodiazepines, heroin (and other opiates),

- Over-bundling

- Autonomic over-activity

- IBD (inflammatory bowel disease) - Crohn's disease/ulcerative colitis

Functional somatic syndromes may occur in 6 to 36% of the population.

Serious complications are uncommon, occurring in less than 5% of cases:

- CNS complications include meningitis, encephalitis, hemiplegia, Guillain–Barré syndrome, and transverse myelitis. Prior infectious mononucleiosis has been linked to the development of multiple sclerosis (MS).

- Hematologic: Hemolytic anemia (direct Coombs test is positive) and various cytopenias, and bleeding (caused by thrombocytopenia) can occur.

- Mild jaundice

- Hepatitis with the Epstein–Barr virus is rare.

- Upper airway obstruction from tonsillar hypertrophy is rare.

- Fulminant disease course of immunocompromised patients is rare.

- Splenic rupture is rare.

- Myocarditis and pericarditis are rare.

- Postural orthostatic tachycardia syndrome

- Chronic fatigue syndrome

- Cancers associated with the Epstein-Barr virus include: Burkitt's lymphoma, Hodgkin's lymphoma and lymphomas in general as well as nasopharyngeal and gastric carcinoma.

Once the acute symptoms of an initial infection disappear, they often do not return. But once infected, the patient carries the virus for the rest of his or her life. The virus typically lives dormantly in B lymphocytes. Independent infections of mononucleosis may be contracted multiple times, regardless of whether the patient is already carrying the virus dormantly. Periodically, the virus can reactivate, during which time the patient is again infectious, but usually without any symptoms of illness. Usually, a patient has few, if any, further symptoms or problems from the latent B lymphocyte infection. However, in susceptible hosts under the appropriate environmental stressors, the virus can reactivate and cause vague physical symptoms (or may be subclinical), and during this phase the virus can spread to others.

Psychological trauma or stress appears to predispose persons to a functional somatic syndrome. HPA axis, autonomic nervous system, and immune response to stress has been proposed as a mediating mechanism. Upper airway resistance syndrome may also be implicated.

It is currently thought that Cogan's syndrome is an autoimmune disease. The inflammation in the eye and ear are due to the patient's own immune system producing antibodies that attack the inner ear and eye tissue. Autoantibodies can be demonstrated in the blood of some patients, and these antibodies have been shown to attack inner ear tissue in laboratory studies. Infection with the bacteria "Chlamydia pneumoniae" has been demonstrated in some patients prior to the development of Cogan's syndrome, leading some researchers to hypothesize that the autoimmune disease may be initiated by the infection. "C. pneumoniae" is a common cause of mild pneumonia, and the vast majority of patients who are infected with the bacteria do not develop Cogan's syndrome.

Some studies have suggested a genetic predisposition to the proposed autoimmune response. Several infectious candidates have been associated with Kikuchi disease.

Many theories exist about the cause of KFD. Microbial/viral or autoimmune causes have been suggested. "Mycobacterium szulgai" and "Yersinia" and "Toxoplasma" species have been implicated. More recently, growing evidence suggests a role for Epstein-Barr virus, as well as other viruses (HHV6, HHV8, parvovirus B19, HIV and HTLV-1) in the pathogenesis of KFD. However, many independent studies have failed to identify the presence of these infectious agents in cases of Kikuchi lymphadenopathy. In addition, serologic tests including antibodies to a host of viruses have consistently proven noncontributory and no viral particles have been identified ultrastructurally.

KFD is now proposed to be a nonspecific hyperimmune reaction to a variety of infectious, chemical, physical, and neoplastic agents. Other autoimmune conditions and manifestations such as antiphospholipid syndrome, polymyositis, systemic juvenile idiopathic arthritis, bilateral uveitis, arthritis and cutaneous necrotizing vasculitis have been linked to KFD. KFD may represent an exuberant T-cell-mediated immune response in a genetically susceptible individual to a variety of nonspecific stimuli.

Human leukocyte antigen class II genes are more frequent in patients with Kikuchi disease, suggesting a genetic predisposition to the proposed autoimmune response.

Night sweats, also known as nocturnal hyperhidrosis, is the occurrence of excessive sweating during sleep. The person may or may not also suffer from excessive perspiration while awake.

One of the most common causes of night sweats in women over 40 is the hormonal changes related to menopause and perimenopause. This is a very common occurrence during the menopausal transition years.

While night sweats might be relatively harmless, it can also be a sign of a serious underlying disease. It is important to distinguish night sweats due to medical causes from those that occur simply because the sleep environment is too warm, either because the bedroom is unusually hot or because there are too many covers on the bed. Night sweats caused by a medical condition or infection can be described as "severe hot flashes occurring at night that can drench sleepwear and sheets, which are not related to the environment". Some of the underlying medical conditions and infections that cause these severe night sweats can be life-threatening and should promptly be investigated by a medical practitioner.

Kikuchi-Fujimoto disease (KFD) is a rare, self-limiting disorder that typically affects the cervical lymph nodes. Recognition of this condition is crucial, especially because it can easily be mistaken for tuberculosis, lymphoma, or even adenocarcinoma. Awareness of this disorder helps prevent misdiagnosis and inappropriate treatment.

Kikuchi's disease is a very rare disease mainly seen in Japan. Isolated cases are reported in North America, Europe, and Asia. It is mainly a disease of young adults (20–30 years), with a slight bias towards females. The cause of this disease is not known, although infectious and autoimmune causes have been proposed. The course of the disease is generally benign and self-limiting. Lymph node enlargmeent usually resolves over several weeks to six months. Recurrence rate is about 3%. Death from Kikuchi disease is extremely rare and usually occurs due to liver, respiratory, or heart failure.

There is no specific treatment for infectious mononucleosis, other than treating the symptoms. In severe cases, steroids such as corticosteroids may be used to control the swelling of the throat and tonsils. Currently, there are no antiviral drugs or vaccines available.

It is important to note that symptoms related to infectious mononucleosis caused by EBV infection seldom last for more than 4 months. When such an illness lasts more than 6 months, it is frequently called chronic EBV infection. However, valid laboratory evidence for continued active EBV infection is seldom found in these patients. The illness should be investigated further to determine if it meets the criteria for chronic fatigue syndrome, or CFS. This process includes ruling out other causes of chronic illness or fatigue.

aHUS can be inherited or acquired, and does not appear to vary by race, gender, or geographic area. As expected with an ultra-rare disease, data on the prevalence of aHUS are extremely limited. A pediatric prevalence of 3.3 cases per million population is documented in one publication of a European hemolytic uremic syndrome (HUS) registry involving 167 pediatric patients.

Cogan's syndrome is a rare, rheumatic disease characterized by inflammation of the ears and eyes. Cogan's syndrome can lead to vision difficulty, hearing loss and dizziness. The condition may also be associated with blood-vessel inflammation (called vasculitis) in other areas of the body that can cause major organ damage in 15% of those afflicted or, in a small number of cases, even death. It most commonly occurs in a person's 20s or 30s. The cause is not known. However, one theory is that it is an autoimmune disorder in which the body's immune system mistakenly attacks tissue in the eye and ear.

About 90% of cases of infectious mononucleosis are caused by the Epstein–Barr virus, a member of the Herpesviridae family of DNA viruses. It is one of the most commonly found viruses throughout the world. Contrary to common belief, the Epstein–Barr virus is not highly contagious. It can only be contracted through direct contact with an infected person’s saliva, such as through kissing or sharing toothbrushes, cups, etc. About 95% of the population has been exposed to this virus by the age of 40, but only 15–20% of teenagers and about 40% of exposed adults actually become infected.

Symptoms of infectious mononucleosis are fever, sore throat, and swollen lymph glands. Sometimes, a swollen spleen or liver involvement may develop. Heart problems or involvement of the central nervous system occurs only rarely, and infectious mononucleosis is almost never fatal. There are no known associations between active EBV infection and problems during pregnancy, such as miscarriages or birth defects. Although the symptoms of infectious mononucleosis usually resolve in 1 or 2 months, EBV remains dormant or latent in a few cells in the throat and blood for the rest of the person's life. Periodically, the virus can reactivate and is commonly found in the saliva of infected persons. Reactivated and post-latent virus may pass the placental barrier in (also seropositive) pregnant women via macrophages and therefore can infect the fetus. Also re-infection of prior seropositive individuals may occur. In contrast, reactivation in adults usually occurs without symptoms of illness.

EBV also establishes a lifelong dormant infection in some cells of the body's immune system. A late event in a very few carriers of this virus is the emergence of Burkitt's lymphoma and nasopharyngeal carcinoma, two rare cancers. EBV appears to play an important role in these malignancies, but is probably not the sole cause of disease.

Most individuals exposed to people with infectious mononucleosis have previously been infected with EBV and are not at risk for infectious mononucleosis. In addition, transmission of EBV requires intimate contact with the saliva (found in the mouth) of an infected person. Transmission of this virus through the air or blood does not normally occur. The incubation period, or the time from infection to appearance of symptoms, ranges from 4 to 6 weeks. Persons with infectious mononucleosis may be able to spread the infection to others for a period of weeks. However, no special precautions or isolation procedures are recommended, since the virus is also found frequently in the saliva of healthy people. In fact, many healthy people can carry and spread the virus intermittently for life. These people are usually the primary reservoir for person-to-person transmission. For this reason, transmission of the virus is almost impossible to prevent.

The clinical diagnosis of infectious mononucleosis is suggested on the basis of the symptoms of fever, sore throat, swollen lymph glands, and the age of the patient. Usually, laboratory tests are needed for confirmation. Serologic results for persons with infectious mononucleosis include an elevated white blood cell count, an increased percentage of certain atypical white blood cells, and a positive reaction to a "mono spot" test.

Treatment is similar to treatment for benign fasciculation syndrome.

Carbamazepine therapy has been found to provide moderate reductions in symptoms.

Atypical hemolytic uremic syndrome (aHUS) has also been referred to as diarrhea-negative hemolytic-uremic syndrome (D HUS).

Post-polio syndrome occurs in approximately 25 to 50 percent of people who survive a poliomyelitis infection. On average, it occurs 30–35 years afterwards; however, delays of between 8–71 years have been recorded. The disease occurs sooner in persons with more severe initial infection. Other factors that increase the risk of postpolio syndrome include increasing length of time since acute poliovirus infection, presence of permanent residual impairment after recovery from the acute illness, and being female.

Post-polio syndrome is documented to occur in cases of nonparalytic polio (NPP). One review states late-onset weakness and fatigue occurs in 14 to 42 percent of NPP patients.

BFS has been reported in other African cultures, and also in Brazil, Argentina, and Ethiopian Jews. Historic higher reported prevalence among males may be due to more males being present in higher education in African countries. Studies since the 1990s have not verified gender differences. Other studies found a possible association with low socioeconomic status, an association with average or higher intelligence, and a high association with neuroticism. Individuals with BFS have been found to have problems with isolation, poor study habits, and the use of psychostimulants as well as physical changes including in muscle tension and heart rate.

The effects of the disease can have profound effects on everyday life. As well, the recurring side effects of excessive belching, dizziness, dry mouth, hangovers, disorientation, irritable bowel syndrome, and chronic fatigue syndrome can lead to other health problems such as depression, anxiety and poor productivity in employment. The random state of intoxication can lead to personal difficulties, and the relative obscurity of the condition can also make it hard to seek treatment.

Pharmacological methods of treatment include fludrocortisone, midodrine, somatostatin, erythropoietin, and other vasopressor agents. However, often a patient with pure autonomic failure can mitigate his or her symptoms with far less costly means. Compressing the legs and lower body, through crossing the legs, squatting, or the use of compression stockings can help. Also, ingesting more water than usual can increase blood pressure and relieve some symptoms.