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Depending on whether the salicylate is a component of food or medicine, salicylate intolerance is a form of food intolerance or of drug intolerance.
Salicylate sensitivity is a pharmacological reaction, not a true IgE-mediated allergy. However, it is possible for aspirin to trigger non-allergic hypersensitivity reactions. About 5–10% of asthmatics have aspirin hypersensitivity, but dietary salicylates have been shown not to contribute to this. The reactions in AERD (Samter's triad) are due to inhibition of the COX-1 enzyme by aspirin, as well as other NSAIDs that are not salicylates. Dietary salicylates have not been shown to significantly affect COX-1.
Samter's triad refers to aspirin sensitivity in conjunction with nasal polyps and asthma.
In various studies, about one half of the patients who seek medical treatment for symptoms of MCS meet the criteria for depressive and anxiety disorders. Because many people eliminate whole categories of food in an effort to reduce symptoms, a complete review of the patient's diet may be needed to avoid nutritional deficiencies.
An important salicylate drug is aspirin, which has a long history. Aspirin intolerance was widely known by 1975, when the understanding began to emerge that it is a pharmacological reaction, not an allergy.
Two small randomized controlled trials (RCTs) and one larger RCT (86 subjects) tested glutamine in the prevention of platinum treatment-induced neuropathy and showed promise. As of September 2013 a larger, placebo-controlled trial is running.
A 2013 systematic review of the use of acetyl-L-carnitine, glutamine, vitamin E, glutathione, vitamin B6, omega-3 fatty acids, magnesium, calcium, alpha lipoic acid and n-acetyl cysteine as anti-CIPN adjuvants concluded that "currently no agent has shown solid beneficial evidence to be recommended for the treatment or prophylaxis of CIPN."
One proposed hypothesis for the cause of multiple chemical sensitivity is immune system dysfunction after being sensitized by a chemical exposure.
As possible preventative interventions, the American National Cancer Institute Symptom Management and Health-related Quality of Life Steering Committee recommends continued investigation of several dietary supplements, including glutathione, and intravenous calcium and magnesium, which have shown early promise in limited human trials; acetyl-L-carnitine, which was effective in animal models and on diabetes and HIV patients; and the anti-oxidant alpha-lipoic acid.
Feline hyperesthesia syndrome is an uncommon but recognized condition in cats, particularly Siamese, Burmese, Himalayan, and Abyssinian cats. It can affect cats of all ages, though it is most prevalent in mature animals. The disease can be somewhat difficult to detect as it is characterized by brief bursts of abnormal behavior, lasting around a minute or two. One of its symptoms is also found in dogs that have canine distemper disease (CD) caused by canine distemper virus (CDV).
OAS must be managed in conjunction with the patient's other allergies, primarily the allergy to pollen. The symptom severity may wax and wane with the pollen levels. Published pollen counts and seasonal charts are useful but may be ineffective in cases of high wind or unusual weather, as pollen can travel hundreds of kilometers from other areas.
In addition, patients are advised to avoid the triggering foods, particularly nuts.
Peeling or cooking the foods has been shown to eliminate the effects of some allergens such as "mal d 1" (apple), but not others such as celery or strawberry. In the case of foods such as hazelnut, which have more than one allergen, cooking may eliminate one allergen but not the other.
Antihistamines may also relieve the symptoms of the allergy by blocking the immune pathway. Persons with a history of severe anaphylactic reaction may carry an injectable emergency dose of epinephrine (such as an EpiPen). Oral steroids may also be helpful. Allergy immunotherapy has been reported to improve or cure OAS in some patients. Immunotherapy with extracts containing birch pollen may benefit OAS sufferers of apple or hazelnut related to birch pollen-allergens. Even so, the increase in the amount of apple/hazelnut tolerated was small (from 12.6 to 32.6 g apple), and as a result, a patient's management of OAS would be limited.
In examining the published studies on opioid-induced hyperalgesia (OIH), Reznikov "et al" criticize the methodologies employed on both humans and animals as being far-removed from the typical regimen and dosages of pain patients in the real world. They also note that some OIH studies were performed on drug addicts in methadone rehabilitation programs, and that such results are very difficult to generalize and apply to medical patients in chronic pain. In contrast, a study of 224 chronic pain patients receiving 'commonly-used' doses of oral opioids, in more typical clinical scenarios, found that the opioid-treated patients actually experienced no difference in pain sensitivity when compared to patients on non-opioid treatments. The authors conclude that opioid-induced hyperalgesia may not be an issue of any significance for normal, medically-treated chronic pain patients at all.
Opioid-induced hyperalgesia has also been criticized as overdiagnosed among chronic pain patients, due to poor differential practice in distinguishing it from the much more common phenomenon of opioid tolerance. The misdiagnosis of common opioid tolerance (OT) as opioid-induced hyperalgesia (OIH) can be problematic as the clinical actions suggested by each condition can be contrary to each other. Patients misdiagnosed with OIH may have their opioid dose mistakenly decreased (in the attempt to counter OIH) at times when it is actually appropriate for their dose to be increased or rotated (as a counter to opioid tolerance).
The suggestion that chronic pain patients who are diagnosed as experiencing opioid-induced hyperalgesia ought to be completely withdrawn from opioid therapy has also been met with criticism. This is not only because of the uncertainties surrounding the diagnosis of OIH in the first place, but because of the viability of rotating the patient between different opioid analgesics over time. Opioid rotation is considered a valid alternative to the reduction or cessation of opioid therapy, and multiple studies demonstrate the rotation of opioids to be a safe and effective protocol.
The College of Optometrists (UK) has specified guidelines for optometrists who use the colorimeter system. A society for coloured lens prescribers has been established to provide a list of eye-care practitioners with expertise in the provision of coloured lenses for the treatment of visual stress.
Desensitization, which is a slow process of eating tiny amounts of the allergenic protein, until the body is able to tolerate more significant exposure, results in reduced symptoms or even remission of the allergy in some people and is being explored for milk allergy. This is called oral immunotherapy (OIT). Sublingual immunotherapy, in which the allergenic protein is held in the mouth, under the tongue, has been approved for grass and ragweed allergies, but not yet for foods. A 2014 meta-analysis found oral desensitization for cow's milk allergy in children to be relatively safe and effective but recommended that further study was needed to understand the overall immune response to it, and questions remain open about duration of the desensitization. Other reviews reached the same conclusion.
There is research - not specific to milk allergy - on probiotics, prebiotics and the combination of the two (synbiotics) as a means of treating or preventing infant and child allergies. From reviews, there appears to be a treatment benefit for eczema, but not asthma, wheezing or rhinoconjunctivitis. The evidence was not consistent. Several reviews concluded that the evidence cannot yet be recommended for clinical practice.
Hyperesthesia (or hyperaesthesia) is a condition that involves an abnormal increase in sensitivity to stimuli of the sense. "When a non-noxious stimulus causes the sensation of pain the area will be termed hyperaesthetic". Stimuli of the senses can include sound that one hears, foods that one tastes, textures that one feels, and so forth. Increased touch sensitivity is referred to as "tactile hyperesthesia", and increased sound sensitivity is called "auditory hyperesthesia". Tactile hyperesthesia may be a common symptom of many neurologic disorders such as herpes zoster, peripheral neuropathy and radiculopathies. In 1979, and then in 1994, Merskey, Bogduk, Noordenbos, Devor and others (a subcommittee of International Association for the Study of Pain) proposed, instead of hyperaesthesia, the concept of allodynia, meaning "other pain", defined as a pain resulting from a stimulus that does not normally provoke pain.
In psychology, Jeanne Siaud-Facchin uses the term by defining it as an "exacerbation des sens" that characterizes gifted children (and adults): for them, the sensory information reaches the brain much faster than the average, and the information is processed in a significantly shorter time.
The disorders have been studied in several institutions, including the Psychology Department at Essex University, the former Applied Psychology Unit, Cambridge University in England, and in the case of Meares-Irlen syndrome, Visual Unit at Glasgow Caledonian University in Scotland. the Visual Stress Unit offered non-commercial diagnostic and therapeutic services to individuals, and provided advice to the Scottish National Health Service.
In Australia, Irlen syndrome was researched by Paul Whiting at the University of Sydney. Whiting set up the first Irlen Dyslexia Centre in Australia, which operated in the Children's Centre at Sydney University for more than 15 years. Irlen syndrome was also studied in Australia by Greg Robinson (1944–2008) at the University of Newcastle. He was director of the Special Education Centre at the School of Education.
In the US, peer-reviewed literature on the topic suggests that much is unknown about the cause of these disorders, ranging from the 2011 study in a journal of the American Academy of Pediatrics, "Irlen Colored Overlays Do not Alleviate Reading Difficulties" and the 2012 study in the journal "Brain Topography", "A Functional Neuroimaging Case Study of Meares–Irlen Syndrome". The first, purely in relation to Meares-Irlen syndrome, finds that there is no evidence for one of the fundamental claims of therapeutic benefit; the second which focused primarily on Irlen syndrome found compelling evidence of unique brain function linked to the syndrome.
Prevention includes avoiding exposure to the sun and wearing sun block on the affected area.
- Cover up: wear long sleeves, slacks, and a wide-brimmed hat whenever harsh exposure is probable
- Avoid chemicals that may trigger a reaction
- Wear sunscreen at least factor 30 with a high UVA protection level
- Wear gloves and/or remain indoors after handling fruits or plants which increase sensitivity to light
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 of opioid tolerance and Opioid-Induced Hyperalgesia (OIH) differs but it may be difficult to differentiate these two conditions in a clinical setting where most pain assessments are done through simple scale scores. The treatment for OIH may be challenging because an inadequate number of quality studies exists possibly due to the complexity in diagnosis of OIH and challenges in working with patients on chronic opioids. Currently there is no single best treatment method for OIH and clinicians are advised to choose an appropriate therapy based on the unique clinical scenario and history of each patient.
One general treatment option is to reduce or discontinue the dose of opioid to see if OIH is improved. Opioid sparing or opioid switching, which is replacing the current opioid with another pharmacological agent such as morphine or methadone, has been reported to be effective in some studies but this may also increase the sensitivity to pain according to some case reports. Ketamine, a NMDA antagonist, has been shown to prevent the extended use of opioid in post-operative hyperalgesia when it is infused in a small amount perioperatively along with the opioid but there are also studies that show ketamine being ineffective in modulating hyperalgesia. Addition of the NSAID, especially some COX-2 inhibitors, or acetaminophen is also suggested as a possible treatment option.
Although genetic factors govern susceptibility to atopic disease, increases in atopy have occurred within too short a time frame to be explained by a genetic change in the population, thus pointing to environmental or lifestyle changes. Several hypotheses have been identified to explain this increased rate; increased exposure to perennial allergens due to housing changes and increasing time spent indoors, and changes in cleanliness or hygiene that have resulted in the decreased activation of a common immune control mechanism, coupled with dietary changes, obesity and decline in physical exercise. The hygiene hypothesis maintains that high living standards and hygienic conditions exposes children to fewer infections. It is thought that reduced bacterial and viral infections early in life direct the maturing immune system away from T1 type responses, leading to unrestrained T2 responses that allow for an increase in allergy.
Changes in rates and types of infection alone however, have been unable to explain the observed increase in allergic disease, and recent evidence has focused attention on the importance of the gastrointestinal microbial environment. Evidence has shown that exposure to food and fecal-oral pathogens, such as hepatitis A, "Toxoplasma gondii", and "Helicobacter pylori" (which also tend to be more prevalent in developing countries), can reduce the overall risk of atopy by more than 60%, and an increased rate of parasitic infections has been associated with a decreased prevalence of asthma. It is speculated that these infections exert their effect by critically altering T1/T2 regulation. Important elements of newer hygiene hypotheses also include exposure to endotoxins, exposure to pets and growing up on a farm.
Some people have reported relief of symptoms by following a low-salicylate diet such as the Feingold diet. Aspirin is quickly converted in the body to salicylic acid, also known as 2-Hydroxybenzoic acid. Sommer "et al." reported a multi-center prospective randomized cross-over trial with 30 patients following a low-salicylate diet for 6 weeks. This study demonstrated a clinically significant decrease in both subjective and objective scoring of severity of disease, but made note of the challenge for patients in following what is a fairly stringent diet.
A diet low in omega-6 oils (precursors of arachidonic acid), and high in omega-3 oils, may also help. In a small study, aspirin-sensitive asthma patients taking 10 grams of fish oil daily reported relief of most symptoms after six weeks, however symptoms returned if the supplement was stopped.
Oat sensitivity represents a sensitivity to the proteins found in oats, "Avena sativa". Sensitivity to oats can manifest as a result of allergy to oat seed storage proteins either inhaled or ingested. A more complex condition affects individuals who have gluten-sensitive enteropathy in which there is also a response to avenin, the glutinous protein in oats similar to the gluten within wheat. Sensitivity to oat foods can also result from their frequent contamination by wheat, barley, or rye particles.
Despite comparisons to panic attack, investigators have identified ataque de nervios as a separate syndrome with measured differences in anxiety sensitivity and types of attacks.
Most people find it necessary to strictly avoid any item containing dairy ingredients. Milk from other species (goat, sheep...) should not be substituted for cow's milk, as milk proteins from other mammals are often cross-reactive. Beyond the obvious (anything with milk, cheese, cream, butter or yogurt in the name), food ingredient lists need to be examined:
- Ghee
- Some Margarine (!)
- Medical food beverages (Ensure, etc.)
- "Non-dairy" coffee creamer
- Eggnog
- Sherbet
- "Cream of..." soups
- Creamy pasta sauces
- Creamy salad dressings
- Nutella
- Simplesse
- Bread
- Baked goods
- Crackers
- Cereals
- Some Chewing gum (!)
- Some Hot dogs (!)
- Instant mashed potatoes
- Flavored potato chips
- Caramel and nougat candy
- casein (milk protein
- whey (milk protein)
- Lactalbumin (milk protein)
- lactoglobulin (milk protein)
- lactoferrin (milk protein)
Probiotic products have been tested, and some found to contain milk proteins which were not always indicated on the labels.
An experimental treatment, enzyme potentiated desensitization (EPD), has been tried for decades but is not generally accepted as effective. EPD uses dilutions of allergen and an enzyme, beta-glucuronidase, to which T-regulatory lymphocytes are supposed to respond by favoring desensitization, or down-regulation, rather than sensitization. EPD has also been tried for the treatment of autoimmune diseases but evidence does not show effectiveness.
A review found no effectiveness of homeopathic treatments and no difference compared with placebo. The authors concluded that, based on rigorous clinical trials of all types of homeopathy for childhood and adolescence ailments, there is no convincing evidence that supports the use of homeopathic treatments.
According to the NCCIH, the evidence is relatively strong that saline nasal irrigation and butterbur are effective, when compared to other alternative medicine treatments, for which the scientific evidence is weak, negative, or nonexistent, such as honey, acupuncture, omega 3's, probiotics, astragalus, capsaicin, grape seed extract, Pycnogenol, quercetin, spirulina, stinging nettle, tinospora or guduchi.
Reported aspects of the syndrome include uncontrollable screaming or shouting, crying, trembling, sensations of heat rising in the chest and head, dissociative experiences, and verbal or physical aggression. The reaction is usually associated with a stressful event relating to the family, although it is not specifically defined as arising from such occurrences.
Allergen immunotherapy (AIT) treatment involves administering doses of allergens to accustom the body to substances that are generally harmless (pollen, house dust mites), thereby inducing specific long-term tolerance. Allergy immunotherapy can be administered orally (as sublingual tablets or sublingual drops), or by injections under the skin (subcutaneous). Discovered by Leonard Noon and John Freeman in 1911, allergy immunotherapy represents the only causative treatment for respiratory allergies.
Experimental research has targeted adhesion molecules known as selectins on epithelial cells. These molecules initiate the early capturing and margination of leukocytes from circulation. Selectin antagonists have been examined in preclinical studies, including cutaneous inflammation, allergy and ischemia-reperfusion injury. There are four classes of selectin blocking agents: (i) carbohydrate based inhibitors targeting all P-, E-, and L-selectins, (ii) antihuman selectin antibodies, (iii) a recombinant truncated form of PSGL-1 immunoglobulin fusion protein, and (iv) small-molecule inhibitors of selectins. Most selectin blockers have failed phase II/III clinical trials, or the studies were ceased due to their unfavorable pharmacokinetics or prohibitive cost. Sphingolipids, present in yeast like "Saccharomyces cerevisiae" and plants, have also shown mitigative effects in animal models of gene knockout mice.
Samter's triad goes by several other names:
A sufferer who has not yet experienced asthma or aspirin sensitivity might be diagnosed as having:
- Non-allergic rhinitis
- Non-allergic rhinitis with eosinophilia syndrome (NARES)