In addition to an OCD or tic disorder diagnosis, children may have other symptoms associated with exacerbations such as emotional lability, enuresis, anxiety, and deterioration in handwriting. In the PANDAS model, this abrupt onset is thought to be preceded by a strep throat infection. As the clinical spectrum of PANDAS appears to resemble that of Tourette's syndrome, some researchers hypothesized that PANDAS and Tourette's may be associated; this idea is controversial and a focus for current research.

Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) is a hypothesis that there exists a subset of children with rapid onset of obsessive-compulsive disorder (OCD) or tic disorders and these symptoms are caused by group A beta-hemolytic streptococcal (GABHS) infections. The proposed link between infection and these disorders is that an initial autoimmune reaction to a GABHS infection produces antibodies that interfere with basal ganglia function, causing symptom exacerbations. It has been proposed that this autoimmune response can result in a broad range of neuropsychiatric symptoms.

The PANDAS hypothesis was based on observations in clinical case studies at the US National Institutes of Health and in subsequent clinical trials where children appeared to have dramatic and sudden OCD exacerbations and tic disorders following infections. There is supportive evidence for the link between "streptococcus" infection and onset in some cases of OCD and tics, but proof of causality has remained elusive. The PANDAS hypothesis is controversial; whether it is a distinct entity differing from other cases of Tourette syndrome (TS)/OCD is debated.

PANDAS has not been validated as a disease entity; it is not listed as a diagnosis by the International Statistical Classification of Diseases and Related Health Problems (ICD) or the "Diagnostic and Statistical Manual of Mental Disorders" (DSM).

A variety of inciting infections have been observed. The most common infection sites are in the upper respiratory tract: including rhinitis, sinusitis, and pharyngitis. The specific microbe most commonly recognized has been group A Streptococcus. Mycoplasma pneumonia, influenza, and other common viruses have also been noted. Influenza has often been well-documented anecdotally at both initial onset and exacerbations of PANS.

A number of additional infections, including gastrointestinal infections, dental infection, herpes simplex, varicella, Epstein-Barr virus, enterovirus, Kawasaki disease, and anaphylactoid purpura, have been mentioned to be associated with the onset or exacerbation of PANS symptoms in a small number of cases.

Additionally, studies have shown a high rate of concurrent autoimmunity in patients with PANS and their first degree family members further supporting a role for inflammation in PANS.

Chorea can also be a manifestation of drug toxicity (for example, anticonvulsants, antiparkinson agents, neuroleptics, steroids, and estrogen), or a result of an infectious disease such as meningovascular syphilis, Lyme disease, viral encephalitis, and many others.

Several pathogenetic mechanisms for chorea gravidarum have been offered, but none have been proven.

History of either rheumatic fever or chorea is suspected: the suggestion is that estrogens and progesterone may sensitize dopamine receptors (presumably at a striatal level) and induce chorea in individuals who are vulnerable to this complication by virtue of preexisting pathology in the basal ganglia.

The relation to rheumatic fever was strengthened by many studies that showed that women with normal pregnancies before rheumatic fever developed chorea in subsequent pregnancies. At least 35% of patients have a definite history of acute rheumatic fever and Sydenham chorea; 4% of those with chorea gravidarum had acute rheumatic fever.

It has been suggested that use of oral contraceptives is an infrequent cause of chorea. A patient developed this chorea with no definite evidence of previous Sydenham's chorea or recent streptoccocal infections, but had anti-basal ganglia antibodies, suggesting immunological basis for the pathophysiology of this chorea.

A person's sex also seems to have some role in the development of autoimmunity; that is, most autoimmune diseases are "sex-related". Nearly 75% of the more than 23.5 million Americans who suffer from autoimmune disease are women, although it is less-frequently acknowledged that millions of men also suffer from these diseases. According to the American Autoimmune Related Diseases Association (AARDA), autoimmune diseases that develop in men tend to be more severe. A few autoimmune diseases that men are just as or more likely to develop as women include: ankylosing spondylitis, type 1 diabetes mellitus, granulomatosis with polyangiitis, Crohn's disease, Primary sclerosing cholangitis and psoriasis.

The reasons for the sex role in autoimmunity vary. Women appear to generally mount larger inflammatory responses than men when their immune systems are triggered, increasing the risk of autoimmunity. Involvement of sex steroids is indicated by that many autoimmune diseases tend to fluctuate in accordance with hormonal changes, for example: during pregnancy, in the menstrual cycle, or when using oral contraception. A history of pregnancy also appears to leave a persistent increased risk for autoimmune disease. It has been suggested that the slight, direct exchange of cells between mothers and their children during pregnancy may induce autoimmunity. This would tip the gender balance in the direction of the female.

Another theory suggests the female high tendency to get autoimmunity is due to an imbalanced X chromosome inactivation. The X-inactivation skew theory, proposed by Princeton University's Jeff Stewart, has recently been confirmed experimentally in scleroderma and autoimmune thyroiditis. Other complex X-linked genetic susceptibility mechanisms are proposed and under investigation.

Tourette syndrome is found among all social, racial and ethnic groups and has been reported in all parts of the world; it is three to four times more frequent among males than among females. The tics of Tourette syndrome begin in childhood and tend to remit or subside with maturity; thus, a diagnosis may no longer be warranted for many adults, and observed prevalence rates are higher among children than adults. As children pass through adolescence, about one-quarter become tic-free, almost one-half see their tics diminish to a minimal or mild level, and less than one-quarter have persistent tics. Only 5 to 14% of adults experience worse tics in adulthood than in childhood.

Up to 1% of the overall population experiences tic disorders, including chronic tics and transient tics of childhood. Chronic tics affect 5% of children, and transient tics affect up to 20%. Prevalence rates in special education populations are higher.

The reported prevalence of TS varies "according to the source, age, and sex of the sample; the ascertainment procedures; and diagnostic system", with a range reported between .4% and 3.8% for children ages 5 to 18. Robertson (2011) says that 1% of school-age children have Tourette's. According to Lombroso and Scahill (2008), the emerging consensus is that .1 to 1% of children have Tourette's, with several studies supporting a tighter range of .6 to .8%. Bloch and Leckman (2009) and Swain (2007) report a range of prevalence in children of .4 to .6%, Knight et al. (2012) estimate .77% in children, and Du et al. (2010) report that 1 to 3% of "Western" school-age children have Tourette's.

Singer (2011) states the prevalence of TS in the overall population at any time is .1% for impairing cases and .6% for all cases, while Bloch and colleagues (2011) state the overall prevalence as between .3 and 1%. Robertson (2011) also suggests that the rate of Tourette's in the general population is 1%. Using year 2000 census data, a prevalence range of .1 to 1% yields an estimate of 53,000–530,000 school-age children with Tourette's in the US, and a prevalence estimate of .1% means that in 2001 about 553,000 people in the UK age 5 or older would have Tourette's.

Tourette syndrome was once thought to be rare: in 1972, the US National Institutes of Health (NIH) believed there were fewer than 100 cases in the United States, and a 1973 registry reported only 485 cases worldwide. However, multiple studies published since 2000 have consistently demonstrated that the prevalence is much higher than previously thought. Discrepancies across current and prior prevalence estimates come from several factors: ascertainment bias in earlier samples drawn from clinically referred cases, assessment methods that may fail to detect milder cases, and differences in diagnostic criteria and thresholds. There were few broad-based community studies published before 2000 and until the 1980s, most epidemiological studies of Tourette syndrome were based on individuals referred to tertiary care or specialty clinics. Individuals with mild symptoms may not seek treatment and physicians may not confer an official diagnosis of TS on children out of concern for stigmatization; children with milder symptoms are unlikely to be referred to specialty clinics, so prevalence studies have an inherent bias towards more severe cases. Studies of Tourette syndrome are vulnerable to error because tics vary in intensity and expression, are often intermittent, and are not always recognized by clinicians, patients, family members, friends or teachers; approximately 20% of persons with Tourette syndrome do not recognize that they have tics. Newer studies—recognizing that tics may often be undiagnosed and hard to detect—use direct classroom observation and multiple informants (parent, teacher, and trained observers), and therefore record more cases than older studies relying on referrals. As the diagnostic threshold and assessment methodology have moved towards recognition of milder cases, the result is an increase in estimated prevalence.

Tourette's is associated with several comorbid conditions, or co-occurring diagnoses, which are often the major source of impairment for an affected child. Most individuals with tics do not seek medical attention, so epidemiological studies of TS "reflect a strong ascertainment bias", but among those who do warrant medical attention, the majority have other conditions, and up to 50% have ADHD or OCD.

A subset of children with acute, rapid-onset of tic disorders and obsessive compulsive disorder (OCD) are hypothesized to be due to an autoimmune response to group A beta-hemolytic streptococcal infection (PANDAS).

Fifty percent of patients with acute Sydenham's chorea spontaneously recover after two to six months whilst mild or moderate chorea or other motor symptoms can persist for up to and over two years in some cases. Sydenham's is also associated with psychiatric symptoms with obsessive compulsive disorder being the most frequent manifestation.

The exact cause of Tourette's is unknown, but it is well established that both genetic and environmental factors are involved. Genetic epidemiology studies have shown that the overwhelming majority of cases of Tourette's are inherited, although the exact mode of inheritance is not yet known and no gene has been identified. In other cases, tics are associated with disorders other than Tourette's, a phenomenon known as "tourettism".

A person with Tourette's has about a 50% chance of passing the gene(s) to one of his or her children, but Tourette's is a condition of variable expression and incomplete penetrance. Thus, not everyone who inherits the genetic vulnerability will show symptoms; even close family members may show different severities of symptoms, or no symptoms at all. The gene(s) may express as Tourette's, as a milder tic disorder (provisional or chronic tics), or as obsessive–compulsive symptoms without tics. Only a minority of the children who inherit the gene(s) have symptoms severe enough to require medical attention. Gender appears to have a role in the expression of the genetic vulnerability: males are more likely than females to express tics.

Non-genetic, environmental, post-infectious, or psychosocial factors—while not causing Tourette's—can influence its severity. Autoimmune processes may affect tic onset and exacerbation in some cases. In 1998, a team at the US National Institute of Mental Health proposed a hypothesis based on observation of 50 children that both obsessive–compulsive disorder (OCD) and tic disorders may arise in a subset of children as a result of a poststreptococcal autoimmune process. Children who meet five diagnostic criteria are classified, according to the hypothesis, as having Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections (PANDAS). This contentious hypothesis is the focus of clinical and laboratory research, but remains unproven. Preliminary evidence suggest that refined sugar, caffeine, and gluten may exacerbate tics.

Some forms of OCD may be genetically linked to Tourette's. A subset of OCD is thought to be causally related to Tourette's and may be a different expression of the same factors that are important for the expression of tics. The genetic relationship of ADHD to Tourette syndrome, however, has not been fully established.

Acute rheumatic fever (ARF) is a complication of respiratory infections caused by GAS. The M-protein generates antibodies that cross-react with autoantigens on interstitial connective tissue, in particular of the endocardium and synovium, that can lead to significant clinical illness.

Although common in developing countries, ARF is rare in the United States, possibly secondary to improved antibiotic treatment, with small isolated outbreaks reported only occasionally. It is most common among children between 5 and 15 years old and occurs 1–3 weeks after an untreated GAS pharyngitis.

ARF is often clinically diagnosed based on Jones Criteria, which include: pancarditis, migratory polyarthritis of large joints, subcutaneous nodules, erythema marginatum, and sydenham chorea (involuntary, purposeless movement). The most common clinical finding is a migratory arthritis involving multiple joints.

Other indicators of GAS infection such as a DNAase or ASO serology test must confirm the GAS infection. Other minor Jones Criteria are fever, elevated ESR and arthralgia. One of the most serious complications is pancarditis, or inflammation of all three heart tissues. A fibrinous pericarditis can develop with a classic friction rub that can be auscultated. This will give increasing pain upon reclining.

Further endocarditis can develop with aseptic vegetations along the valve closure lines, in particular the mitral valve. Chronic rheumatic heart disease mostly affects the mitral valve, which can become thickened with calcification of the leaflets, often causing fusion of the commissures and chordae tendineae.

Other findings of ARF include erythema marginatum (usually over the spine or other bony areas) and a red expanding rash on the trunk and extremities that recurs over weeks to months. Because of the different ways ARF presents itself, the disease may be difficult to diagnose.

A neurological disorder, Sydenham chorea, can occur months after an initial attack, causing jerky involuntary movements, muscle weakness, slurred speech, and personality changes. Initial episodes of ARF as well as recurrences can be prevented by treatment with appropriate antibiotics.

It is important to distinguish ARF from rheumatic heart disease. ARF is an acute inflammatory reaction with pathognomonic Aschoff bodies histologically and RHD is a non-inflammatory sequela of ARF.

A major manifestation of acute rheumatic fever, Sydenham's chorea is a result of an autoimmune response that occurs following infection by group A β-hemolytic streptococci that destroys cells in the corpus striatum of the basal ganglia. Molecular mimicry to streptococcal antigens leading to an autoantibody production against the basal ganglia has long been thought to be the main mechanism by which chorea occurs in this condition. In 2012, antibodies in serum to the cell surface antigen; dopamine 2 receptor were shown in up to a third of patients in a cohort of Sydenham's chorea. Whether these antibodies represent an epi-phenomenon or are pathogenic, remains to be proven.

There are many causes of childhood chorea, including cerebrovascular accidents, collagen vascular diseases, drug intoxication, hyperthyroidism, Wilson's disease, Huntington's disease, abetalipoproteinemia, Fahr disease, biotin-thiamine-responsive basal ganglia disease due to mutations in the SLC19A3 gene, Lesch-Nyhan syndrome, and infectious agents.

Prognosis is poor, however, current analysis suggests that those associated with thymoma, benign or malignant, show a less favorable prognosis (CASPR2 Ab positive).

An immune disorder is a dysfunction of the immune system. These disorders can be characterized in several different ways:

- By the component(s) of the immune system affected

- By whether the immune system is overactive or underactive

- By whether the condition is congenital or acquired

According to the International Union of Immunological Societies, more than 150 primary immunodeficiency diseases (PIDs) have been characterized. However, the number of acquired immunodeficiencies exceeds the number of PIDs.

It has been suggested that most people have at least one primary immunodeficiency. Due to redundancies in the immune system, though, many of these are never detected.

Most common cause of autoimmune encephalitis after acute demyelinating encephalitis in England. More than 500 cases have been reported in literature till 2013. In California Encephalitis Project it was found >4 times as frequently as herpes simplex virus type 1 (HSV-1), varicella-zoster virus (VZV), and West Nile virus (WNV). Among patients with first-onset schizophrenia incidence varies between 6–10%.

- Age – frequently 5–76 years, Median age of patients was 23 years

- Sex – 80% Female

An allergy is an abnormal immune reaction to a harmless antigen.

- Seasonal allergy

- Mastocytosis

- Perennial allergy

- Anaphylaxis

- Food allergy

- Allergic rhinitis

- Atopic dermatitis

An interesting inverse relationship exists between infectious diseases and autoimmune diseases. In areas where multiple infectious diseases are endemic, autoimmune diseases are quite rarely seen. The reverse, to some extent, seems to hold true. The hygiene hypothesis attributes these correlations to the immune manipulating strategies of pathogens. While such an observation has been variously termed as spurious and ineffective, according to some studies, parasite infection is associated with reduced activity of autoimmune disease.

The putative mechanism is that the parasite attenuates the host immune response in order to protect itself. This may provide a serendipitous benefit to a host that also suffers from autoimmune disease. The details of parasite immune modulation are not yet known, but may include secretion of anti-inflammatory agents or interference with the host immune signaling.

A paradoxical observation has been the strong association of certain microbial organisms with autoimmune diseases.

For example, "Klebsiella pneumoniae" and coxsackievirus B have been strongly correlated with ankylosing spondylitis and diabetes mellitus type 1, respectively. This has been explained by the tendency of the infecting organism to produce super-antigens that are capable of polyclonal activation of B-lymphocytes, and production of large amounts of antibodies of varying specificities, some of which may be self-reactive (see below).

Certain chemical agents and drugs can also be associated with the genesis of autoimmune conditions, or conditions that simulate autoimmune diseases. The most striking of these is the drug-induced lupus erythematosus. Usually, withdrawal of the offending drug cures the symptoms in a patient.

Cigarette smoking is now established as a major risk factor for both incidence and severity of rheumatoid arthritis. This may relate to abnormal citrullination of proteins, since the effects of smoking correlate with the presence of antibodies to citrullinated peptides.

Neurodevelopmental disorders are in their multitude associated with widely varying degrees of difficulty, depending on which there are different degrees of mental, emotional, physical, and economic consequences for individuals, and in turn families, groups and society.

Other genetic causes of chorea are rare. They include the classical Huntington's disease 'mimic' or phenocopy syndromes, called Huntington's disease-like syndrome types 1, 2 and 3; inherited prion disease, the spinocerebellar ataxias type 1, 3 and 17, neuroacanthocytosis, dentatorubral-pallidoluysian atrophy (DRPLA), brain iron accumulation disorders, Wilson's disease, benign hereditary chorea, Friedreich's ataxia, mitochondrial disease and Rett syndrome.

Immune reactions during pregnancy, both maternal and of the developing child, may produce neurodevelopmental disorders. One typical immune reaction in infants and children is PANDAS, or "Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection". Another disorder is Sydenham's chorea, which results in more abnormal movements of the body and fewer psychological sequellae. Both are immune reactions against brain tissue that follow infection by "Streptococcus" bacteria. Susceptibility to these immune diseases may be genetically determined, so sometimes several family members may suffer from one or both of them following an epidemic of Strep infection.

Although the cause of SS is unknown, it is believed to be under the influence of a combination of genetic, environmental, and several other factors, as is the case with many other autoimmune disorders.

The observation of high rates of autoimmune disorders in families of SS is linked with a genetic predisposition to the syndrome. Studies on the polymorphisms of human leukocyte antigen (HLA)-DR and HLA-DQ gene regions in SS patients show differential susceptibility to the syndrome due to different types of the resulting autoantibody production.

An individual may only develop signs of an infection after a period of subclinical infection, a duration that is called the incubation period. This is the case, for example, for subclinical sexually transmitted diseases such as AIDS and genital warts. Individuals with such subclinical infections, and those that never develop overt illness, creates a reserve of individuals that can transmit an infectious agent to infect other individuals. Because such cases of infections do not come to clinical attention, health statistics can often fail to measure the true prevalence of an infection in a population, and this prevents the accurate modeling of its infectious transmission.

Huntington's disease is a neurodegenerative disease and the most common inherited cause of chorea. The condition was formerly called Huntington's chorea but was renamed because of the important non-choreic features including cognitive decline and behavioural change.