A 2008 literature review concluded that, "From the evidence-based perspective, there is conflicting evidence whether there is or is not an association between coeliac disease or auto-antibodies and epilepsy. As yet there is no compelling evidence that there is a causal relation. There probably is a specific syndrome—coeliac disease with epilepsy and calcifications—which is rare and perhaps geographically specific."

At least one study suggests that gluten neuropathy can be effectively treated with a gluten-free diet. In the study, 35 patients with gluten neuropathy adhered to a gluten-free diet, where adherence was monitored serologically. After one year, the treatment group had improved significantly compared to the control group. The indicators of improvements were improvements of sural sensory action potential and subjective improvement of neuropathic symptoms. Subgroup analysis suggested that severe neuropathy might imply reduced capacity for recovery of the peripheral nerves or longer recovery.

Fibromyalgia was found in 9% of adult patients relative to 0.03% in the general population with a link common to IBD. Concurrent IBS is found in 30% to 70%. Small intestinal bacterial overgrowth is associated is common with a transient response to antimicrobial therapy.

Some instance of arthritis with small bowel villous atrophy have been found to resolve

on gluten free diet, and anti-connective tissue antibodies have been found in increased levels in celiac disease. Anti-rheumatoid factor antibodies are also increased. In addition, cross-reactive anti-beef-collagen antibodies (IgG) may explain some "rheumatoid arthritis" (RA) incidences. Although the presence of anti-beef collagen antibodies does not necessarily lead to RA, the RA association with "Triticeae" consumption is secondary to GSE and involves DRB1*0401/4 linkages to DQ8 and is debatable. In one instance rhuematoid arthritis was tied directly to refractory disease.

At present, the only effective treatment is a lifelong gluten-free diet. No medication exists that will prevent damage or prevent the body from attacking the gut when gluten is present. Strict adherence to the diet allows the intestines to heal, leading to resolution of all symptoms in most cases and, depending on how soon the diet is begun, can also eliminate the heightened risk of osteoporosis and intestinal cancer and in some cases sterility. The diet can be cumbersome; failure to comply with the diet may cause relapse.

Dietitian input is generally requested to ensure the person is aware which foods contain gluten, which foods are safe, and how to have a balanced diet despite the limitations. In many countries, gluten-free products are available on prescription and may be reimbursed by health insurance plans. Gluten-free products are usually more expensive and harder to find than common gluten-containing foods. Since ready-made products often contain traces of gluten, some coeliacs may find it necessary to cook from scratch.

The term "gluten-free" is generally used to indicate a supposed harmless level of gluten rather than a complete absence. The exact level at which gluten is harmless is uncertain and controversial. A recent systematic review tentatively concluded that consumption of less than 10 mg of gluten per day is unlikely to cause histological abnormalities, although it noted that few reliable studies had been done. Regulation of the label "gluten-free" varies. In the European Union, the European Commission issued regulations in 2009 limiting the use of "gluten-free" labels for food products to those with less than 20 mg/kg of gluten, and "very low gluten" labels for those with less than 100 mg/kg. In the United States, the FDA issued regulations in 2013 limiting the use of "gluten-free" labels for food products to those with less than 20 ppm of gluten. The current international Codex Alimentarius standard allows for 20 ppm of gluten in so-called "gluten-free" foods. Several organisations, such as the Gluten-Free Certification Organization (GFCO), the Celiac Sprue Association (CSA), and the National Foundation for Celiac Awareness (NFCA), also certify products and companies as gluten-free.

Gluten-free diet improves healthcare-related quality of life, and strict adherence to the diet gives more benefit than incomplete adherence. Nevertheless, gluten-free diet doesn't completely normalise the quality of life.

Between 0.3% and 10% of people have refractory disease, which means that they have persistent villous atrophy on a gluten-free diet despite the lack of gluten exposure for more than 12 months. Nevertheless, inadvertent exposure to gluten is the main cause of persistent villous atrophy, and must be ruled out before a diagnosis of refractory disease is made. People with poor basic education and understanding of gluten-free diet often believe that they are strictly following the diet, but are making regular errors. Also, a lack of symptoms is not a reliable indicator of intestinal recuperation.

If alternative causes of villous atrophy have been eliminated, steroids or immunosuppressants (such as azathioprine) may be considered in this scenario.

Refractory coeliac disease should not be confused with the persistence of symptoms despite gluten withdrawal caused by transient conditions derived from the intestinal damage, which generally revert or improve several months after starting a gluten-free diet, such as small intestinal bacterial overgrowth, lactose intolerance, fructose, sucrose, and sorbitol malabsorption, exocrine pancreatic insufficiency, and microscopic colitis, among others.

There are many open questions on gluten sensitivity, emphasized in one review that "it is still to be clarified whether this disorder is permanent or transient and whether it is linked to autoimmunity". It has not yet been established whether innate or adaptive immune responses are involved in NCGS, nor whether the condition relates specifically to gluten or rather relates to other components of grains.

Studies indicate that AGA IgG is high in slightly more than half of NCGS patients and that, unlike for celiac disease patients, the IgG AGA decreases strongly over 6 months of gluten-free diet; AGA IgA is usually low or absent in NCGS patients.

The need for developing biomarkers for NCGS is frequently emphasized; for example, one review indicated: "There is a desperate need for reliable biomarkers ... that include clinical, biochemical and histopathological findings which support the diagnosis of NCGS."

A 2014 preliminary study found "that short-term exposure to gluten can induce depressive symptoms in people with non-celiac gluten sensitivity".

Research has also attempted to discern, by double-blind placebo-controlled trials, between a "fad component" to the recent popularity of the gluten-free diet and an actual sensitivity to gluten or other components of wheat. In a double-blind placebo cross-over trial, small amounts of purified wheat gluten triggered gastrointestinal symptoms (such as abdominal bloating and pain) and extra-intestinal manifestations (such as foggy mind, depression and aphthous stomatitis) in self-reported NCGS. Nevertheless, it remains elusive whether these findings specifically implicate gluten or proteins present in gluten-containing cereals.

Approximately one third of presumed NGCS patients continue to have symptoms, despite gluten withdrawal. Apart from a possible diagnostic error, there are multiple possible explanations.

One reason is poor compliance with gluten withdrawal, whether voluntary and/or involuntary. There may be ingestion of gluten, in the form of cross contamination or food containing hidden sources. In some cases, the amelioration of gastrointestinal symptoms with a gluten-free diet is only partial, and these patients could significantly improve with the addition of a low-FODMAPs diet.

A subgroup may not improve when eating commercially available gluten-free products, as these can be rich in preservatives and additives such as sulfites, glutamates, nitrates and benzoates, which can also have a role in triggering functional gastrointestinal symptoms. Furthermore, people with NCGS may often present with IgE-mediated allergies to one or more foods. It has been estimated that around 35% suffer other food intolerances, mainly lactose intolerance.

Once a diagnosis of JDMS is made, the treatment is often a 3-day course of Intravenous ("pulse") steroids (methylprednisolone, Solu-Medrol), followed by a high dose of oral prednisone (usually 1–2 mg/kg of body weight) for several weeks. This action usually brings the disease under control, lowering most lab tests to or near normal values. Some minor improvement in muscle symptoms may also be seen in this time, but normally it takes a long time for full muscle strength to be regained.

Once the disease process is under control, oral steroids are tapered gradually to minimize their side effects. Often, steroid-sparing drugs, such as methotrexate (a chemotherapy drug) or other DMARDs, are given to compensate for the reduction in oral steroids. Once the oral steroids are reduced to a less toxic level, the sparing agents can also be gradually withdrawn. Lab results are closely monitored during the tapering process to ensure that the disease does not recur.

In the cases where steroids or second-line drugs are not tolerated or are ineffective, there are other treatments that can be tried. These include other chemotherapy drugs, such as ciclosporin, infliximab, or other DMARDs. Another is intravenous immunoglobulin (IVIg), a blood product that has been shown to be very effective against JDMS.

To treat the skin rash, anti-malarial drugs, such as hydroxychloroquine (Plaquenil) are usually given. Topical steroid creams (hydrocortisone) may help some patients, and anti-inflammatory creams (such as tacrolimus) are proving to be very effective. Dry skin caused by the rash can be combated by regular application of sunscreen or any moisturizing cream. Most JDM patients are very sensitive to sun exposure, and sunburn may be a disease activity trigger in some, so daily application of high-SPF sunscreen is often recommended.

Of the children diagnosed with and treated for JDM, about half will recover completely. Close to 30 percent will have weakness after the disease resolves. Most children will go into remission and have their medications eliminated within two years, while others may take longer to respond or have more severe symptoms that take longer to clear up.

A common lasting effect of JDM is childhood arthritis.

For patients with celiac disease, a lifelong strict gluten-free diet is the only effective treatment to date; for patients diagnosed with NCGS, there are still open questions concerning for example the duration of such a diet; for patients with wheat allergy, the individual average is six years of gluten-free diet, excepting persons with anaphylaxis, for whom the diet is to be wheat-free for life.

A gluten-free diet should not be started before the tests for excluding celiac disease have been performed, for the reason that the serological and biopsy tests for celiac disease are reliable only if the patient is consuming gluten.

Preferably, newly diagnosed celiacs seek the help of a dietician to receive support for identifying hidden sources of gluten, planning balanced meals, reading labels, food shopping, dining out, and dining during travel. Knowledge of hidden sources of gluten is important for celiac disease patients as they need to be very strict regarding eating only gluten-free food; for NCGS patients, it is not certain how strict the diet needs to be. Balanced eating is important because unless particular care is taken, a gluten-free diet can be lacking in vitamins, minerals, and fiber, and be too high in fat and calories.

The inclusion of oats in gluten-free diets remains controversial. Avenin present in oats may also be toxic for coeliac sufferers. Its toxicity depends on the cultivar consumed. Furthermore, oats are frequently cross-contaminated with gluten-containing cereals.

Changes in inflammatory cells affect the body, which reduces the intake of "nutrients, fat-soluble vitamins and minerals" in the body.

Liver transplantation has proven to be effective for ATTR familial amyloidosis due to Val30Met mutation.

Alternatively, a European Medicines Agency approved drug Tafamidis or Vyndaqel now exists which stabilizes transthyretin tetramers comprising wild type and different mutant subunits against amyloidogenesis halting the progression of peripheral neuropathy and autonomic nervous system dysfunction.

Currently there are two ongoing clinical trials undergoing recruitment in the United States and worldwide to evaluate investigational medicines that could possibly treat TTR.

There is a great deal of conflicting information regarding the inclusion of oats in a gluten-free diet. Although cross-contamination in the field and during processing partially explains the different reactions that celiacs can have to oats, a recent study indicates that there are also different amounts of avenin present in different cultivars of oat. The G12 antibody used in the study is currently the only one that can reliably distinguish between varieties of oat. Previous studies have indicated both children and adult coeliacs are largely tolerant of oats. Other studies have followed both children and adults for one, two, and five years on the "uncontaminated" oat containing gluten-free diet. These studies failed to show significant changes in intestinal morphology indicative of a relapse of celiac disease. Anti-gliadin and reticulin antibodies as well as numbers of intraepithelial lymphocytes (IELs) did not differ significantly between oat-eating celiacs and non-oat-eating controls in remission. Invitro tests that are sensitive to wheat gluten found that tryptic peptides of avenin could not induce EMA production in supernatant fluid from cultured duodenal mucosa specimen from celiac patients.

Algorithms that successfully predict T cell stimulatory peptides in gluten identified many similar peptides in hordeins and secalins, but not in oat avenins.

The Canadian Celiac Association suggests that adults can consume up to 70g of oats per day, and children up to 25g. However, two studies indicated that celiac adults could consume 93 grams (3.3 ounces) of oats per day. There is no evidence that oats can trigger GSE, only that in a small number of celiacs disease can be sustained or reinitiated by oats once triggered by wheat. A recent paper examining the IEL levels of celiac patients in remission showed a significantly higher number of IELs in oat-eating celiacs. In addition, antibodies to avenin remain low as long as the diet is gluten-free, but higher anti-avenin antibodies can increase with a diet containing wheat.

Some coeliacs respond adversely to oats. Estimates range from 0.5 to 20% of the GSE population. With coeliac disease, non-compliance in attempting to achieve normal intestinal morphology is a risk factor for refractory disease and cancer.

Treatment is primarily through diet. Dietary fiber and fat can be increased and fluid intake, especially fruit juice intake, decreased. With these considerations, the patient should consume a normal balanced diet to avoid malnutrition or growth restriction. Medications such as loperamide should not be used. Studies have shown that certain probiotic preparations such as "Lactobacillus rhamnosus" (a bacterium) and "Saccharomyces boulardii" (a yeast) may be effective at reducing symptoms.

Treatment is based on the underlying cause, if any. Where the likely underlying condition is known, treatment of this condition is indicated treated to reduce progression of the disease and symptoms. For cases without those conditions, there is only symptomatic treatment.

Dermatitis herpetiformis generally responds well to medication and changes in diet. However, it is an autoimmune disease, and patients with DH are more likely than others to have thyroid problems and intestinal lymphoma.

Dermatitis herpetiformis does not usually cause complications on its own, without being associated with another condition. Complications from this condition, however, arise from the autoimmune character of the disease, as an overreacting immune system is a sign that something does not work well and might cause problems to other parts of the body that do not necessarily involve the digestive system.

Gluten intolerance and the body's reaction to it make the disease more worrying in what concerns the possible complications. This means that complications that may arise from dermatitis herpetiformis are the same as those resulting from coeliac disease, which include osteoporosis, certain kinds of gut cancer, and an increased risk of other autoimmune diseases such as thyroid disease.

The risks of developing complications from dermatitis herpetiformis decrease significantly if the affected individuals follow a gluten-free diet. The disease has been associated with autoimmune thyroid disease, insulin-dependent diabetes, lupus erythematosus, Sjögren's syndrome, sarcoidosis, vitiligo, and alopecia areata.

Dapsone is an effective treatment in most people. Itching is typically reduced within 2–3 days. However, dapsone treatment has no effect on any intestinal damage that might be present.

Therefore, a strict gluten-free diet must also be followed, and this will usually be a lifelong requirement. This will reduce any associated intestinal damage and the risk of other complications. After some time on a gluten-free diet, the dosage of dapsone can usually be reduced or even stopped, although this can take many years.

Dapsone is an antibacterial, and its role in the treatment of DH, which is not caused by bacteria, is poorly understood. It can cause adverse effects on the blood, so regular blood monitoring is required.

Dapsone is the drug of choice. For individuals with DH unable to tolerate dapsone for any reason, alternative treatment options may include the following:

- colchicine

- lymecycline

- nicotinamide

- tetracycline

- sulfamethoxypyridazine

- sulfapyridine

A Low FODMAP diet now has an evidence base sufficiently strong to recommend its widespread application in conditions such as IBS and IBD. Restriction of Fermentable Oligo-, Di- and Mono-

saccharides and Polyols globally, rather than individually, controls the symptoms of functional gut disorders (e.g. IBS), and the majority of IBD patients respond just as well. It is more successful than restricting only Fructose and Fructans, which are also FODMAPs, as is recommended for those with Fructose malabsorption. Longer term compliance with the diet was high.

A randomised controlled trial on IBS patients found relaxing an IgG-mediated food intolerance diet led to a 24% greater deterioration in symptoms compared to those on the elimination diet and concluded food elimination based on IgG antibodies may be effective in reducing IBS symptoms and is worthy of further biomedical research.

Intestinal or bowel hyperpermeability, so called leaky gut, has been linked to food allergies and some food intolerances. Research is currently focussing on specific conditions and effects of certain food constituents. At present there are a number of ways to limit the increased permeability, but additional studies are required to assess if this approach reduces the prevalence and severity of specific conditions.

Gluten-sensitive enteropathy and its common and more severe form, coeliac disease, results in the increased inflammation of the tissues of the small bowel, eventually leading to villus atrophy. The disease progresses from increased lymphocyte counts to eventual flattening of the villi, and crypt hyperplasia. Originally, oats were believed to cause coeliac disease. However, this confusion was largely due to significant contamination of oats with wheat, barley, or rye. A recent review of controlled oat tolerance studies indicated only one documented avenin-sensitive enteropathy (ASE) in 165, placing the risk of ASE at 0.6% of the coeliac disease population. However, during the controlled studies, 17 candidates dropped out due to symptoms after ingestion of gluten-free oats and were not tested at the completion of their respective studies. As a result, the actual risk of ASE in the coelic disease population may be slightly higher.

Treatment is with penicillin, ampicillin, tetracycline, or co-trimoxazole for one to two years. Any treatment lasting less than a year has an approximate relapse rate of 40%. Recent expert opinion is that Whipple's disease should be treated with doxycycline with hydroxychloroquine for 12 to 18 months. Sulfonamides (sulfadiazine or sulfamethoxazole) may be added for treatment of neurological symptoms.

Those diseases understood as congenital in origin could either be specific to the ocular organ system (LHON, DOA) or syndromic (MELAS, Multiple Sclerosis). It is estimated that these inherited optic neuropathies in the aggregate affect 1 in 10,000

Of the acquired category, disease falls into further etiological distinction as arising from toxic (drugs or chemicals) or nutritional/metabolic (vitamin deficiency/diabetes) insult. It is worth mentioning that under-nutrition and toxic insult can occur simultaneously, so a third category may be understood as having a combined or mixed etiology. We will refer to this as Toxic/Nutritional Optic Neuropathy, whereby nutritional deficiencies and toxic/metabolic insults are the simultaneous culprits of visual loss associated with damage and disruption of the RGC and optic nerve mitochondria.

There are many possible causes of small fiber neuropathy. The most common cause is diabetes or glucose intolerance. Other possible causes include hypothyroidism, Sjögren's syndrome, Lupus, vasculitis, sarcoidosis, nutritional deficiency, Celiac disease, Lyme disease, HIV, Fabry disease, amyloidosis and alcoholism. A 2008 study reported that in approximately 40% of patients no cause could be determined after initial evaluation. When no cause can be identified, the neuropathy is called idiopathic. A recent study revealed dysfunction of a particular sodium channel (Nav1.7) in a significant portion of the patient population with an idiopathic small fiber neuropathy.

Recently several studies have suggested an association between autonomic small fiber neuropathy and postural orthostatic tachycardia syndrome. Other notable studies have shown a link between erythromelalgia, and fibromyalgia.

SFN is a common feature in adults with Ehlers-Danlos Syndrome (EDS). Skin biopsy could be considered an additional diagnostic tool to investigate pain manifestations in EDS.

AIP often completely resolves with steroid treatment. The failure to differentiate AIP from malignancy may lead to unnecessary pancreatic resection, and the characteristic lymphoplasmacytic infiltrate of AIP has been found in up to 23% of patients undergoing pancreatic resection for suspected malignancy who are ultimately found to have benign disease. In this subset of patients, a trial of steroid therapy may have prevented a Whipple procedure or complete pancreatectomy for a benign disease which responds well to medical therapy. "This benign disease resembles pancreatic carcinoma both clinically and radiographically. The diagnosis of autoimmune pancreatitis is challenging to make. However, accurate and timely diagnosis may preempt the misdiagnosis of cancer and decrease the number of unnecessary pancreatic resections." Autoimmune pancreatitis responds dramatically to corticosteroid treatment.

If relapse occurs after corticosteroid treatment or corticosteroid treatment is not tolerated, immunomodulators may be used. Immunomodulators such as azathioprine, and 6-mercaptopurine have been shown to extend remission of autoimmune pancreatitis after corticosteroid treatment. If corticosteroid and immunomodulator treatments are not sufficient, rituximab may also be used. Rituximab has been shown to induce and maintain remission.

A range of medications that act on the central nervous system has been found to be useful in managing neuropathic pain. Commonly used treatments include tricyclic antidepressants (such as nortriptyline or amitriptyline), the serotonin-norepinephrine reuptake inhibitor (SNRI) medication duloxetine, and antiepileptic therapies such as gabapentin, pregabalin, or sodium valproate. Few studies have examined whether nonsteroidal anti-inflammatory drugs are effective in treating peripheral neuropathy.

Symptomatic relief for the pain of peripheral neuropathy may be obtained by application of topical capsaicin. Capsaicin is the factor that causes heat in chili peppers. The evidence suggesting that capsaicin applied to the skin reduces pain for peripheral neuropathy is of moderate to low quality and should be interpreted carefully before using this treatment option. Local anesthesia often is used to counteract the initial discomfort of the capsaicin. Some current research in animal models has shown that depleting neurotrophin-3 may oppose the demyelination present in some peripheral neuropathies by increasing myelin formation.

High-quality evidence supports the use of cannabis for neuropathic pain.