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.

According to the hygiene hypothesis, high levels of cleanliness expose children to fewer antigens than in the past, causing their immune systems to become overactive and more likely to misidentify own tissues as foreign, resulting in autoimmune conditions such as asthma.

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.

The first estimate of US prevalence for autoimmune diseases as a group was published in 1997 by Jacobson, et al. They reported US prevalence to be around 9 million, applying prevalence estimates for 24 diseases to a US population of 279 million. Jacobson's work was updated by Hayter & Cook in 2012. This study used Witebsky's postulates, as revised by Rose & Bona, to extend the list to 81 diseases and estimated overall cumulative US prevalence for the 81 autoimmune diseases at 5.0%, with 3.0% for males and 7.1% for females. The estimated community

prevalence, which takes into account the observation that many people have more than one autoimmune disease, was 4.5% overall, with 2.7% for males and 6.4% for females.

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.

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.

An autoimmune disease is a condition arising from an abnormal immune response to a normal body part. There are at least 80 types of autoimmune diseases. Nearly any body part can be involved. Common symptoms include low grade fever and feeling tired. Often symptoms come and go.

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.

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.

Autoimmune hepatitis has an incidence of 1-2 per 100,000 per year, and a prevalence of 10-20/100,000. As with most other autoimmune diseases, it affects women much more often than men (70%). Liver enzymes are elevated, as may be bilirubin.

Autoimmune hepatitis is not a benign disease. Despite a good initial response to immunosuppression, recent studies suggest that the life expectancy of patients with autoimmune hepatitis is lower than that of the general population. Additionally, presentation and response to therapy appears to differ according to race. For instance, African Americans appear to present with a more aggressive disease that is associated with worse outcomes.

There is no clear obvious cause for scleroderma and systemic sclerosis. Genetic predisposition appears to be limited: genetic concordance is small; still, there is often a familial predisposition for autoimmune disease. Polymorphisms in "COL1A2" and "TGF-β1" may influence severity and development of the disease. There is limited evidence implicating cytomegalovirus (CMV) as the original epitope of the immune reaction, as well as parvovirus B19. Organic solvents and other chemical agents have been linked with scleroderma.

One of the suspected mechanisms behind the autoimmune phenomenon is the existence of microchimerism, i.e. fetal cells circulating in maternal blood, triggering an immune reaction to what is perceived as foreign material.

A distinct form of scleroderma and systemic sclerosis may develop in patients with chronic renal failure. This form, nephrogenic fibrosing dermopathy or nephrogenic systemic fibrosis, has been linked to exposure to gadolinium-containing radiocontrast.

Bleomycin (a chemotherapeutic agent) and possibly taxane chemotherapy may cause scleroderma, and occupational exposure to solvents has been linked with an increased risk of systemic sclerosis.

These are also referred to as systemic autoimmune diseases. The autoimmune CTDs may have both genetic and environmental causes. Genetic factors may create a predisposition towards developing these autoimmune diseases. They are characterized as a group by the presence of spontaneous overactivity of the immune system that results in the production of extra antibodies into the circulation. The classic collagen vascular diseases have a "classic" presentation with typical findings that doctors can recognize during an examination. Each also has "classic" blood test abnormalities and abnormal antibody patterns. However, each of these diseases can evolve slowly or rapidly from very subtle abnormalities before demonstrating the classic features that help in the diagnosis. The classic collagen vascular diseases include:

- Systemic lupus erythematosus (SLE) – An inflammation of the connective tissues, SLE can afflict every organ system. It is up to nine times more common in women than men and strikes black women three times as often as white women. The condition is aggravated by sunlight.

- Rheumatoid arthritis – Rheumatoid arthritis is a systemic disorder in which immune cells attack and inflame the membrane around joints. It also can affect the heart, lungs, and eyes. Of the estimated 2.1 million Americans with rheumatoid arthritis, approximately 1.5 million (71 percent) are women.

- Scleroderma – an activation of immune cells that produces scar tissue in the skin, internal organs, and small blood vessels. It affects women three times more often than men overall, but increases to a rate 15 times greater for women during childbearing years, and appears to be more common among black women.

- Sjögren's syndrome – also called Sjögren's disease, is a chronic, slowly progressing inability to secrete saliva and tears. It can occur alone or with rheumatoid arthritis, scleroderma, or systemic lupus erythematosus. Nine out of 10 cases occur in women, most often at or around mid-life.

- Mixed connective tissue disease – Mixed connective-tissue disease (MCTD) is a disorder in which features of various connective-tissue diseases (CTDs) such as systemic lupus erythematosus (SLE); systemic sclerosis (SSc); dermatomyositis (DM); polymyositis (PM); anti-synthetase syndrome; and, occasionally, Sjögren syndrome can coexist and overlap. The course of the disease is chronic and usually milder than other CTDs. In most cases, MCTD is considered an intermediate stage of a disease that eventually becomes either SLE or Scleroderma.

- Undifferentiated connective tissue disease (UCTD) is a disease in which the body mistakenly attacks its own tissues. It is diagnosed when there is evidence of an existing autoimmune condition which does not meet the criteria for any specific autoimmune disease, such as systemic lupus erythematosus or scleroderma. Latent lupus and incomplete lupus are alternative terms that have been used to describe this condition.

- Psoriatic arthritis is also a collagen vascular disease.

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.

Scleroderma in pregnancy is a complex situation; it increases the risk to both mother and child. Overall scleroderma is associated with reduced fetal weight for gestational age. The treatment for scleroderma often includes known teratogens such as cyclophosphamide, methotrexate, mycophenolate, etc. and hence careful avoidance of such drugs during pregnancy is advised. In these cases hydroxychloroquine and low-dose corticosteroids might be used for disease control.

A connective tissue disease is any disease that has the connective tissues of the body as a target of pathology. Connective tissue is any type of biological tissue with an extensive extracellular matrix that supports, binds together, and protects organs. These tissues form a framework, or matrix, for the body, and are composed of two major structural protein molecules: collagen and elastin. There are many different types of collagen protein in each of the body's tissues. Elastin has the capability of stretching and returning to its original length—like a spring or rubber band. Elastin is the major component of ligaments (tissues that attach bone to bone) and skin. In patients with connective tissue disease, it is common for collagen and elastin to become injured by inflammation (ICT). Many connective tissue diseases feature abnormal immune system activity with inflammation in tissues as a result of an immune system that is directed against one's own body tissues (autoimmunity).

Diseases in which inflammation or weakness of collagen tends to occur are also referred to as collagen diseases. Collagen vascular diseases can be (but are not necessarily) associated with collagen and blood vessel abnormalities and that are autoimmune in nature. See also vasculitis.

Connective tissue diseases can have strong or weak inheritance risks, and can also be caused by environmental factors.

All patients with symptomatic cryoglobulinemia are advised to avoid, or protect their extremities, from exposure to cold temperatures. Refrigerators, freezers, and air-conditioning represent dangers of such exposure.

Periodic fever syndromes (also known as autoinflammatory diseases or autoinflammatory syndromes) are a set of disorders characterized by recurrent episodes of systemic and organ-specific inflammation. Unlike autoimmune disorders such as systemic lupus erythematosus, in which the disease is caused by abnormalities of the adaptive immune system, patients with autoinflammatory diseases do not produce autoantibodies or antigen-specific T or B cells. Instead, the autoinflammatory diseases are characterized by errors in the innate immune system.

The syndromes are diverse, but tend to cause episodes of fever, joint pains, skin rashes, abdominal pains and may lead to chronic complications such as amyloidosis.

Most autoinflammatory diseases are genetic and present during childhood. The most common genetic autoinflammatory syndrome is familial Mediterranean fever, which causes short episodes of fever, abdominal pain, serositis, lasting less than 72 hours. It is caused by mutations in the MEFV gene, which codes for the protein pyrin.

Pyrin is a protein normally present in the inflammasome. The mutated pyrin protein is thought to cause inappropriate activation of the inflammasome, leading to release of the pro-inflammatory cytokine IL-1β. Most other autoinflammatory diseases also cause disease by inappropriate release of IL-1β. Thus, IL-1β has become a common therapeutic target, and medications such as anakinra, rilonacept, and canakinumab have revolutionized the treatment of autoinflammatory diseases.

However, there are some autoinflammatory diseases that are not known to have a clear genetic cause. This includes PFAPA, which is the most common autoinflammatory disease seen in children, characterized by episodes of fever, aphthous stomatitis, pharyngitis, and cervical adenitis. Other autoinflammatory diseases that do not have clear genetic causes include adult-onset Still's disease, systemic-onset juvenile idiopathic arthritis, Schnitzler syndrome, and chronic recurrent multifocal osteomyelitis. It is likely that these diseases are multifactorial, with genes that make people susceptible to these diseases, but they require an additional environmental factor to trigger the disease.

Another example that shows that autoinflamatory conditions may not be genetic in origin is found in a report published in "Nature" which shows that diet is very important in the development of such diseases. The ingestion levels of highly saturated fats and cholesterol, (high fat diet, HFD) affects the microbiota composition of the gut. Changes in the microbiota induced by a HFD are protective against the susceptibility to develop osteomyelitis (autoimmune disease) as compared with the changes induced by a low-fat diet. The changes in the microbiome of individuals under HFD showed a reduction in "Prevotella" abundance and were accompanied by significantly reduced expression levels of pro-Interleukin-1β in distant neutrophils.

Scleromyositis or the PM/Scl overlap syndrome is a complex autoimmune disease (a disease in which the immune system attacks the body). Patients with scleromyositis have symptoms of both systemic scleroderma and either polymyositis or dermatomyositis, and is therefore considered an overlap syndrome. Although it is a rare disease, it is one of the more common overlap syndromes seen in scleroderma patients, together with MCTD and Antisynthetase syndrome. Autoantibodies often found in these patients are the anti-PM/Scl (anti-exosome) antibodies.

The symptoms that are seen most often are typical symptoms of the individual autoimmune diseases and include Raynaud's phenomenon, arthritis, myositis and scleroderma. Treatment of these patients is therefore strongly dependent on the exact symptoms with which a patient reports to a physician and is similar to treatment for the individual autoimmune disease, often involving either immunosuppressive or immunomodulating drugs.

- Clinical characteristics:

- Overlap Syndrome: scleroderma overlap syndrome

- Autoimmune disease

- Scleroderma myositis overlap syndrome

Scleroderma overlap syndrome: Scleroderma is a connective tissue disease that causes fibrosis and vascular abnormalities, but that also has an autoimmune component.

It is described by connective tissues complications. Blood testing includes screening for the positive antinuclear antibody.

Patients have symptoms of both systemic scleroderma and/or polymyositis and dermatomyositis.

1. Scleroderma: a group of rare diseases that involve the hardening and tightening of the skin and connective tissues

and/or:

Polymyositis: a rare inflammatory disease that causes muscle weakness affecting both sides of your body

Dermatomyositis: an inflammatory disease of skin and muscle marked especially by muscular weakness and skin rash.

Individuals found to have circulating cryoglobulins but no signs or symptoms of cryoglobulinemic diseases should be evaluated for the possibility that their cryoglobulinemia is a transient response to a recent or resolving infection. Those with a history of recent infection that also have a spontaneous and full resolution of their cryoglobulinemia need no further treatment. Individuals without a history of infection and not showing resolution of their cryoglobulinemia need to be further evaluated. Their cryoglobulins should be analyzed for their composition of immunoglobulin type(s) and complement component(s) and examined for the presence of the premalignant and malignant diseases associated with Type I disease as well as the infectious and autoimmune diseases associated with type II and type III disease. A study conducted in Italy on >140 asymptomatic individuals found five cases of hepatitis C-related and one case of hepatitis b-related cryoglobulinemia indicating that a complete clinical examination of asymptomatic individuals with cryoglobulinemia offers a means for finding people with serious but potentially treatable and even curable diseases. Individuals who show no evidence of a disease underlying their cryoglobulinemia and who remain asymptomatic should be followed closely for any changes that may indicate development of cryoglobulinemic disease.

The 5-year survival rate for scleroderma is about 85%, whereas the 10-year survival rate is less than 70%. This varies according to the subtype; for instance, persons with limited skin disease have a 10-year survival rate of 71%, whereas the outlook for patients with systemic scleroderma has generally improved over the years. Ten-year survival rates rose from 54% in 1972 to 66% in 2001 The major causes of death in persons with scleroderma are: pulmonary hypertension, pulmonary fibrosis and scleroderma renal crisis. People with scleroderma are also at a heightened risk for contracting cancers (especially liver, lung, haematologic and bladder cancers) and, perhaps, cardiovascular disease.

Systemic scleroderma is a rare disease with an annual incidence of 1 to 2 per 100,000 individuals in the United States. The interval of peak onset starts at age 30 to 35 and ends at age 50 to 55.

In the United States, the prevalence of systemic scleroderma is about 50,000, with different studies giving different estimates, usually ranging between 40,000 and 165,000.

Annual incidence of systemic sclerosis is 19 per million, and prevalence is 19–75 per 100,000, with a female:male ratio of 3:1 (8:1 in mid- to late childbearing years). Incidence is twice as high among African Americans. The Choctaw Native Americans in Oklahoma have the highest prevalence in the world (469 per 100,000).

The disease has some hereditary association. It may also be caused by an immune reaction to a virus (molecular mimicry) or by toxins.

The prevalence and incidence of Devic's disease has not been established, partly because the disease is underrecognized and often confused with MS. Devic's disease is more common in women than men, with women comprising over two-thirds of patients and more than 80% of those with the relapsing form of the disease.

A retrospective study found that prevalence of NMOsd was 1.5% inside a random sample of neurological patients, with a MS:NMOsd ratio of 42.7. Among 13 NMOsd patients, 77% had long spinal cord lesions, 38% had severe optic neuritis and 23% had brain or brainstem lesions. Only 56% had clinically definite NMO at follow-up.

According to the Walton Centre in England, "NMO seems to be present across the world unlike MS, which has a higher incidence in temperate climates and white races. Africans and Asians especially in Far East may have a higher risk of NMO, although the exact incidence of this disease is unknown, making specific conclusions difficult". Although many people who have Devic's disease were initially misdiagnosed with MS, 35% of African Americans are often misdiagnosed with MS when they really have NMO.

Devic's disease is more common in Asians than Caucasians. In fact, Asian optic-spinal MS (which constitutes 30% of the cases of MS in Japan) has been suggested to be identical to Devic's disease (differences between optic-spinal and classic MS in Japanese patients). In the indigenous populations of tropical and subtropical regions, MS is rare, but when it appears, it often takes the form of optic-spinal MS.

The majority of Devic's disease patients have no affected relatives, and it is generally regarded as a nonfamilial condition.

Normally, some measure of improvement appears in a few weeks, but residual signs and disability may persist, sometimes severely.

The disease can be monophasic, i.e. a single episode with permanent remission. However, at least 85% of patients have a relapsing form of the disease with repeated attacks of transverse myelitis and/or optic neuritis. In patients with the monophasic form, the transverse myelitis and optic neuritis occur simultaneously or within days of each other. On the other hand, patients with the relapsing form are more likely to have weeks or months between the initial attacks, and to have better motor recovery after the initial transverse myelitis event. Relapses usually occur early, with about 55% of patients having a relapse in the first year and 90% in the first five years.

It is possible that the relapsing form is related to the antiAQP4+ seropositive status and the monophasic form related to its absence Unlike multiple sclerosis, Devic's disease rarely has a secondary progressive phase in which patients have increasing neurologic decline between attacks without remission. Instead, disabilities arise from the acute attacks.

Approximately 20% of patients with monophasic Devic's disease have permanent visual loss, and 30% have permanent paralysis in one or both legs. Among patients with relapsing Devic's disease, 50% have paralysis or blindness within five years. In some patients (33% in one study), transverse myelitis in the cervical spinal cord resulted in respiratory failure and subsequent death. However, the spectrum of Devic's disease has widened due to improved diagnostic criteria, and the options for treatment have improved; as a result, researchers believe these estimates will be lowered.