While it is recognized that there is probably a genetic disposition in certain individuals for the development of autoimmune diseases, the rate of increase in incidence of autoimmune diseases is not a result of genetic changes in humans; the increased rate of autoimmune-related diseases in the industrialized world is occurring in too short a time to be explained in this way. There is evidence that one of the primary reasons for the increase in autoimmune diseases in industrialized nations is the significant change in environmental factors over the last century. Environmental factors include exposure to certain artificial chemicals from industrial processes, medicines, farming, and food preparation. It is posited that the absence of exposure to certain parasites, bacteria, and viruses is playing a significant role in the development of autoimmune diseases in the more sanitized and industrialized Western nations.

Lack of exposure to naturally occurring pathogens and parasites may result in an increased incidence of autoimmune diseases. Correlational data has shown the prevalence of helminthic infections to be greatest south of the equator where the rates of autoimmune diseases such as multiple sclerosis are low.

This is consistent with the hygiene hypothesis which suggests that helminthic infections protect individuals from developing auto-immune diseases rather than being an agent responsible for inducing them. A complete explanation of how environmental factors play a role in autoimmune diseases has still not been proposed. Epidemiological studies such as the meta-analysis by Leonardi-Bee et al., however, have helped to establish the link between parasitic infestation and their protective role in autoimmune disease development.

Genetic research on the interleukin genes (IL genes) shows that helminths have been a major selective force on a subset of these human genes. In other words, helminths have shaped the evolution of at least parts of the human immune system, especially the genes responsible for Crohn's disease, ulcerative colitis, and celiac disease; and provides further evidence that it is the absence of parasites, and in particular helminths, that has likely caused a substantial portion of the increase in incidence of diseases of immune dysregulation and inflammation in industrialized countries in the last century. A systematic approach was used to determine the relative pressure pathogens, such as helminths, viruses or bacteria exerted upon a selection of interleukin genes. Fumagalli et al. (2009) examined 52 globally dispersed human populations along with the diverse levels of pathogen richness, for >650,00 SNPs within 91 IL or IL receptor genes. Helminths were identified as a major selective pressure on a subset of IL genes. Through additional genome-wide association studies the subset of IL genes were associated with the human susceptibility to IBS and coeliac disease.

Helminths are extremely successful parasites capable of establishing long-lasting infections within a host. During this time, helminths compete with the host organism's cells for nutrient resources and thus possess the potential to cause harm. However, the number of organisms hosted by individuals undergoing helminthic therapy is very small and any side effects are typically only encountered in the first three months of infection. In the long term, the vast majority of clinically infected individuals are asymptomatic, with no significant nutrient loss. In fact, nutrient uptake can be enhanced in some subjects who are hosting a small number of helminths. If the side effects from helminthic therapy were to become unmanageable, they can be alleviated by the use of anthelminthic medications.[1][7][8] The most common clinical symptoms which may be encountered while undergoing helminthic therapy can include:

- Fatigue

- Gastrointestinal discomfort

- Anemia

- Fever

- Abdominal pain

- Weight loss

- Anorexia

- Diarrhea

- General malaise

Latest estimates indicate that the total annual death toll which is directly attributable is as high as 135,000. The death toll due to the malnutrition link is likely to be much higher.

The World Health Organization estimates that globally more than 1.5 billion people (24% of the total population) have a soil-transmitted helminth infection. Over 270 million preschool-age children and over 600 million school-age children live in areas where these parasites are intensively transmitted, and are in need of treatment and preventive interventions. Latest estimates indicate that more than 880 million children are in need of treatment from STH infections.

By type of parasitic worm the breakdown is:

- approximately 807-1,121 million with ascaris

- approximately 576-740 million with hookworm

- approximately 604-795 million with whipworm

"A. cantonensis" and its vectors are endemic to Southeast Asia and the Pacific Basin. The infection is becoming increasingly important as globalization allows it to spread to more and more locations, and as more travelers encounter the parasites. The parasites probably travel effectively through rats traveling as stowaways on ships, and through the introduction of snail vectors outside endemic areas.

Although mostly found in Asia and the Pacific where asymptomatic infection can be as high as 88%, human cases have been reported in the Caribbean, where as much as 25% of the population may be infected. In the United States, cases have been reported in Hawaii, which is in the endemic area [5]. The infection is now endemic in wildlife and a few human cases have also been reported in areas where the parasite was not originally endemic, such as New Orleans and Egypt.

The disease has also arrived in Brazil, where there were 34 confirmed cases from 2006 to 2014, including one death. The giant African land snail, which can be a vector of the parasite, has been introduced to Brazil as an invasive species and is spreading the disease. There may be more undiagnosed cases, as Brazilian physicians are not familiar with the eosinophilic meningitis associated to angiostrongyliasis and misdiagnose it as bacterial or viral.

There are many public health strategies that can drastically limit the transmission of "A. cantonensis" by limiting contact with infected vectors. Vector control may be possible, but has not been very successful in the past. Education to prevent the introduction of rats or snail vectors outside endemic areas is important to limit the spread of the disease. There are no vaccines in development for angiostrongyliasis.

Amphistomiasis in farm and wild mammals is due to infection of paramphistomes, such as the species of "Paramphistomum", "Calicophoron", "Cotylophoron", "Pseudophisthodiscus", etc. These are essentially rumen flukes, of which "Paramphistomum cervi" is the most notorious in terms of prevalence and pathogenicity. Infection occurs through ingestion of contaminated vegetables and raw meat, in which the viable infective metacercaria are deposited from snails, which are the intermediate hosts. The immature flukes are responsible for destroying the mucosal walls of the alimentary tract on their way to growing into adults. It is by this fervent tissue obliteration that the clinical symptoms are manifested. The adult flukes, on the other hand, are quite harmless, as they merely prepare for reproduction.

The zoonotic infection in human is caused by "G. discoides" and "W. watsoni" which are essentially intestinal flukes. The disease due to "G. discoides" is more specifically termed gastrodiscoidiasis. In their natural hosts such as pigs and monkeys, their infection in asymptomatic, but human infection is prevalent, by which they cause serious health problems, characterised by diarrhoea, fever, abdominal pain, colic, and an increased mucous production. In extreme situations such as in Assam, India, a number of mortality among children is attributed to this disease.

Humans are accidental hosts of "Toxocara", yet toxocariasis is seen throughout the world. Most cases of toxocariasis are seen in people under the age of twenty. Seroprevalence is higher in developing countries, but can be considerable in first world countries, as well. In Bali, St. Lucia, Nepal and other countries, seroprevalence is over fifty percent. Previous to 2007, the U.S. seroprevalence was thought to be around 5% in children. However, Won et al. discovered that U.S. seroprevalence is actually 14% for the population at large. In many countries, toxocariasis is considered very rare. Approximately 10,000 clinical cases are seen a year in the U.S., with ten percent being OLM. Permanent vision loss occurs in 700 of these cases.

Young children are at the greatest risk of infection because they play outside and tend to place contaminated objects and dirt in their mouths. Dog ownership is another known risk factor for transmission. There is also a significant correlation between high "Toxocara" antibody titers and epilepsy in children.

Parasitic loads as high as 300 larvae in a single gram of liver have been noted in humans. The “excretory-secretory antigens of larvae… released from their outer epicuticle coat [and]… readily sloughed off when bound by specific antibodies” incite the host’s immune response. The tipping point between development of VLM and OLM is believed to be between 100 and 200 larvae. The lighter infection in OLM is believed to stimulate a lower immune response and allow for migration of a larva into the eye. Larvae are thought to enter the eye through the optic nerve, central retinal artery, short posterior ciliary arteries, soft tissues, or cerebrospinal fluid. Ocular granulomas that form around a larva typically are peripheral in the retina or optic disc.

Visceral larva migrans seems to affect children aged 1–4 more often while ocular larva migrans more frequently affects children aged 7–8. Between 4.6% and 23% of U.S. children have been infected with the dog roundworm egg. This number is much higher in other parts of the world, such as Colombia, where up to 81% of children have been infected.

Amphistomiasis or paramphistomiasis (alternatively spelled amphistomosis or paramphistomosis) is a parasitic disease of livestock animals, more commonly of cattle and sheep, and humans caused by immature helminthic flatworms belonging to the order Echinostomida. The term amphistomiasis is used for broader connotation implying the disease inflicted by members of Echinostomida including the family Paramphistomidae/Gastrodiscidae (to be precise, the species "Gastrodiscoides hominis"); whereas paramphistomiasis is restricted to that of the members of the family Paramphistomatidae only. "G. discoides" and "Watsonius watsoni" are responsible for the disease in humans, while most paramphistomes are responsible in livestock animals, and some wild mammals. In livestock industry the disease causes heavy economic backlashes due to poor production of milk, meat and wool.

Actively involving veterinarians and pet owners is important for controlling the transmission of "Toxocara" from pets to humans. A group very actively involved in promoting a reduction of infections in dogs in the United States is the Companion Animal Parasite Council -- CAPC. Since pregnant or lactating dogs and cats and their offspring have the highest, active parasitic load, these animals should be placed on a deworming program. Pet feces should be picked up and disposed of or buried, as they may contain "Toxocara" eggs. Practicing this measure in public areas, such as parks and beaches, is especially essential for decreasing transmission. Up to 20% of soil samples of U.S. playgrounds have found roundworm eggs. Also, sandboxes should be covered when not in use to prevent cats from using them as litter boxes. Hand washing before eating and after playing with pets, as well as after handling dirt will reduce the chances of ingesting "Toxocara" eggs. Washing all fruits and vegetables, keeping pets out of gardens and thoroughly cooking meats can also prevent transmission. Finally, teaching children not to place nonfood items, especially dirt, in their mouths will drastically reduce the chances of infection.

Toxocariasis has been named one of the neglected diseases of U.S. poverty, because of its prevalence in Appalachia, the southern U.S., inner city settings, and minority populations. Unfortunately, there is currently no vaccine available or under development. However, the mitochondrial genomes of both "T. cati" and "T. canis" have recently been sequenced, which could lead to breakthroughs in treatment and prevention.

Both experimental and epidemiological evidence strongly implicates "Opisthorchis viverrini" infections in the etiology of a malignant cancer of the bile ducts (cholangiocarcinoma) in humans which has a very poor prognosis. "Clonorchis sinensis" and "Opisthorchis viverrini" are both categorized by the International Agency for Research on Cancer (IARC) as Group 1 carcinogens.

In humans, the onset of cholangiocarcinoma occurs with chronic opisthorchiasis, associated with hepatobiliary damage, inflammation, periductal fibrosis and/or cellular responses to antigens from the infecting fluke. These conditions predispose to cholangiocarcinoma, possibly through an enhanced susceptibility of DNA to damage by carcinogens. Chronic hepatobiliary damage is reported to be multi-factorial and considered to arise from a continued mechanical irritation of the epithelium by the flukes present, particularly via their suckers, metabolites and excreted/secreted antigens as well as immunopathological processes. "In silico" analyses using techniques of genomics and bioinformatics is unraveling information on molecular mechanisms that may be relevant to the development of cholangiocarcinoma.

In regions where "Opisthorchis viverrini" is highly endemic, the incidence of cholangiocarcinoma is unprecedented. For instance, cholangiocarcinomas represent 15% of primary liver cancer worldwide, but in Thailand's Khon Kaen region, this figure escalates to 90%, the highest recorded incidence of this cancer in the world. Of all cancers worldwide from 2002, 0.02% were cholangiocarcinoma caused by "Opisthorchis viverrini". The cancer of the bile ducts caused by opisthorchiasis occur in the ages 25–44 years in Thailand. A few cases have appeared in later life among veterans of the Vietnam war in the United States, who consumed poorly cooked fish from streams in endemic areas near the border of Laos and Vietnam.

Opisthorchiasis is prevalent where raw cyprinid fishes are a staple of the diet. Prevalence rises with age; children under the age of 5 years are rarely infected by "Opisthorchis viverrini". Males may be affected more than females. The WHO estimates that foodborne trematodiases (infection by worms or "flukes", mainly "Clonorchis", "Opisthorchis", "Fasciola" and "Paragonimus" species) affect 56 million people worldwide and 750 million are at risk of infection. Eighty million are at risk of opisthorchiasis, 67 million from infection with "Opisthorchis viverrini" in Southeast Asia and 13 million from "Opisthorchis felineus" in Kazakhstan, Russia including Siberia, and Ukraine. In the lower Mekong River basin, the disease is highly endemic, and more so in lowlands, with a prevalence up to 60% in some areas of northeast Thailand. However, estimates using newer polymerase chain reaction-based diagnostic techniques indicate that prevalence is probably grossly underestimated. In one study from the 1980s, a prevalence of over 90% was found in persons greater than 10 years old in a small village near Khon Kaen in northeast Thailand in the region known as Isaan. Sporadic cases have been reported in case reports from Malaysia, Singapore, and the Philippines. Although overall prevalence declined after initial surveys in the 1950s, increases since the 1990s in some areas seem associated with large increases in aquaculture.

CLM can be treated in a number of different ways:

- Systemic (oral) agents include albendazole (trade name "Albenza") and ivermectin (trade name "Stromectol")).

- Another agent which can be applied either topically "or" taken by mouth is thiabendazole (trade name "Mintezol")), an anti-helminthic.

- Topical freezing agents, such as ethylene chloride or liquid nitrogen, applied locally can freeze and kill the larvae, but this method has a high failure rate because the larvae are usually located away from the site of the visible skin trails. Additionally, this is a painful method which can cause blistering and/or ulceration of the skin and it is therefore not recommended.

- It is recommended to use Benadryl or some anti-itch cream (i.e. Cortizone or Calamine lotion). This will help relieve some of the itch.

- Wearing shoes in areas where these parasites are known to be endemic offers protection from infection. In general, avoiding exposure of skin to contaminated soil or sand offers the best protection. In some areas dogs have been banned from beaches in an attempt to control human infection.

Cutaneous larva migrans (abbreviated CLM) is a skin disease in humans, caused by the larvae of various nematode parasites of the hookworm family (Ancylostomatidae). The most common species causing this disease in the Americas is "Ancylostoma braziliense". These parasites live in the intestines of dogs, cats, and wild animals and should not be confused with other members of the hookworm family for which humans are definitive hosts, namely "Ancylostoma duodenale" and "Necator americanus".

Colloquially called creeping eruption due to its presentation, the disease is also somewhat ambiguously known as "ground itch" or (in some parts of the Southern USA) "sandworms", as the larvae like to live in sandy soil. Another vernacular name is plumber's itch. The medical term CLM literally means "wandering larvae in the skin".

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.

The increased incidence of Crohn's in the industrialized world indicates an environmental component. Crohn's is associated with an increased intake of animal protein, milk protein and an increased ratio of omega-6 to omega-3 polyunsaturated fatty acids.

Those who consume vegetable proteins appear to have a lower incidence of Crohn's disease. Consumption of fish protein has no association.

Smoking increases the risk of the return of active disease (flares). The introduction of hormonal contraception in the United States in the 1960s is associated with a dramatic increase in incidence, and one hypothesis is that these drugs work on the digestive system in ways similar to smoking. Isotretinoin is associated with Crohn's. Although stress is sometimes claimed to exacerbate Crohn's disease, there is no concrete evidence to support such claim. Dietary microparticles, such as those found in toothpaste, have been studied as they produce effects on immunity, but they were not consumed in greater amounts in patients with Crohn's.

The percentage of people with Crohn's disease has been determined in Norway and the United States and is similar at 6 to 7.1:100,000. The Crohn's and Colitis Foundation of America cites this number as approx 149:100,000; NIH cites 28 to 199 per 100,000. Crohn's disease is more common in northern countries, and with higher rates still in the northern areas of these countries. The incidence of Crohn's disease is thought to be similar in Europe but lower in Asia and Africa. It also has a higher incidence in Ashkenazi Jews and smokers.

Crohn's disease begins most commonly in people in their teens and 20s, and people in their 50s through to their 70s. It is rarely diagnosed in early childhood. It usually affects female children more severely than males. However, only slightly more women than men have Crohn's disease. Parents, siblings or children of people with Crohn's disease are 3 to 20 times more likely to develop the disease. Twin studies find that if one has the disease there is a 55% chance the other will too.

The incidence of Crohn's disease is increasing in Europe.

IBD resulted in a global total of 51,000 deaths in 2013 and 55,000 deaths in 1990. The increased incidence of IBD since World War 2 has been linked to the increase in meat consumption worldwide, supporting the claim that animal protein intake is associated with IBD. Inflammatory bowel diseases are increasing in Europe.

DUSN may be caused by a helminthic infection with Toxocara canis, Baylisascaris procyonis, or Ancylostoma caninum. The characteristic lesions are believed to result from a single nematode migrating within the subretinal space. Although previously thought to be endemic in some areas, that belief was likely due to under awareness. DUSN has been diagnosed in patients in many countries and climates including America, Brazil, China and India.

While IBD can limit quality of life because of pain, vomiting, diarrhea, and other socially undesired symptoms, it is rarely fatal on its own. Fatalities due to complications such as toxic megacolon, bowel perforation and surgical complications are also rare..

Around one-third of individuals with IBD experience persistent gastrointestinal symptoms similar to irritable bowel syndrome (IBS) in the absence of objective evidence of disease activity. Despite enduring the side-effects of long-term therapies, this cohort has a quality of life that is not significantly different to that of individuals with uncontrolled, objectively active disease, and escalation of therapy to biological agents is typically ineffective in resolving their symptoms. The cause of these IBS-like symptoms is unclear, but it has been suggested that changes in the gut-brain axis, epithelial barrier dysfunction, and the gut flora may be partially responsible.

While patients of IBD do have an increased risk of colorectal cancer, this is usually caught much earlier than the general population in routine surveillance of the colon by colonoscopy, and therefore patients are much more likely to survive.

New evidence suggests that patients with IBD may have an elevated risk of endothelial dysfunction and coronary artery disease.

A recent literature review by Gandhi et al. described that IBD patients over the age of 65 and females are at increased risk of coronary artery disease despite the lack of traditional risk factors.

The goal of treatment is toward achieving remission, after which the patient is usually switched to a lighter drug with fewer potential side effects. Every so often, an acute resurgence of the original symptoms may appear; this is known as a "flare-up". Depending on the circumstances, it may go away on its own or require medication. The time between flare-ups may be anywhere from weeks to years, and varies wildly between patients – a few have never experienced a flare-up.

Life with IBD can be challenging, however, it should not impede your ability to live a normal life. Patients with IBD can go to college, hold a normal job, get married, have children etc. As is the nature of any chronic, unpredictable disease, there will be ups and downs. The progress made in IBD research and treatment is astounding and will only improve in the years to come.

Although living with IBD can be difficult, there are numerous resources available to help families navigate the ins and out of IBD. The Crohn's and Colitis Foundation of America (CCFA) is an excellent resource. CCFA is a vital resource to getting questions answered and finding support about life with IBD.

Research has not revealed any difference in overall risk of dying in patients with ulcerative colitis from that of the background population. The cause-of-death distribution may be different from that of the background population. It is thought that the disease primarily affects quality of life, and not lifespan.

Many hypotheses have been raised for environmental factors contributing to the pathogenesis of ulcerative colitis. They include the following:

- Diet: as the colon is exposed to many dietary substances which may encourage inflammation, dietary factors have been hypothesized to play a role in the pathogenesis of both ulcerative colitis and Crohn's disease. Few studies have investigated such an association; one study showed no association of refined sugar on the prevalence of ulcerative colitis. High intake of unsaturated fat and vitamin B6 may enhance the risk of developing ulcerative colitis. Other identified dietary factors that may influence the development and/or relapse of the disease include meat protein and alcoholic beverages. Specifically, sulfur has been investigated as being involved in the etiology of ulcerative colitis, but this is controversial. Sulfur restricted diets have been investigated in patients with UC and animal models of the disease. The theory of sulfur as an etiological factor is related to the gut microbiota and mucosal sulfide detoxification in addition to the diet.

- Breastfeeding: Some reports of the protection of breastfeeding in the development of inflammatory bowel disease contradict each other. One Italian study showed a potential protective effect.

- One study of isotretinoin found a small increase in the rate of ulcerative colitis.

Several aetiologies are suggested, and any combination of these may be present in any given case.

- Vitamin deficiency (A, B or C)

- Viral infection

- Bacterial infection

- "Leptospira

- "Streptococcus

- "Brucella

- Parasitic infection

- Strongyle

- "Onchocerca cervicalis"

- Autoimmune disease

The disease has been suggested to be primarily autoimmune in nature, being a delayed hypersensitivity reaction to any of the above agents.

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 Appaloosa has a higher risk of developing ERU than other breeds; this predisposition has a genetic basis. Appaloosas which develop ERU are more likely than other breeds to have ERU in both eyes, and more likely to become blind in one or both eyes.