November 2014: Post summaries and take home points

Food allergy series: Atopy, risk factors and frequency

  • Food allergy generally refers to IgE mediated reactions in literature
  • Other reactions can cause severe food reactions via different mechanisms
  • Food allergy reacts to specific allergen following skin or mucosal contact (mouth, GI tract)
  • Sensitization is when your body makes IgE to something.
  • Allergy is when your body makes IgE to something and that thing makes you sick.
  • Atopy is the tendency of a person to develop allergic diseases like asthma.
  • The term “allergic march” describes progressive accumulation of atopic conditions starting in the first year of life.
  • Allergic march usually begins with atopic dermatitis and progresses to allergic rhinitis, asthma, and food allergy.
  • Severe eczema developed in the first six months of life is associated with increased risk of peanut, milk and egg allergies.
  • Most food allergies are due to egg, cow’s milk, wheat, soy, shellfish, peanuts and tree nuts.
  • 4% of children with food allergies have multiple food allergies.
  • Children with multiple food allergies are most likely to have severe reactions.
  • Adolescents ages 14-17 are more likely to have severe reactions.
  • Peanut, cashews, walnuts and shellfish allergies are most likely to be severe.
  • Largest studies on food allergy use patient reported information which is not the most reliable.
  • Many people eliminate foods from their diets based upon suspicion of allergy. This is usually unnecessary.
  • 89% of patients with atopic dermatitis were shown to have no reactions to suspect foods on oral challenge.
  • 4% of US households had children with multiple food allergies.
  • 3% of US households had children with history of severe allergic reaction.
  • In Canadian households, 8% of people have food allergies.
  • In Australia, 3% of children are allergic to peanuts and 8.9% are allergic to raw eggs.
  • Risk factors for food allergies include:
  • Atopy
  • Low vitamin D
  • Reduced consumption of omega-3 polyunsaturated fatty acids
  • Reduced consumption of antioxidants
  • Increased use of antacids
  • Obesity
  • Increased hygiene
  • Delaying exposure to common allergens
  • Family history of food allergies
  • Specific HLA profiles
  • Male children are more likely to develop food allergies.
  • Black children are most likely to develop food allergies, followed by Asian children, then White children.
  • Children of immigrants in the US are at higher risk than children of American born parents.
  • People living in households earning more than $50,000/yr are more likely to be diagnosed with food allergies.
  • Childhood allergies to milk, egg, wheat and soy are more likely to resolve.
  • Childhood allergies to peanut, tree nut, fish and shellfish are more likely to persist.

MTHFR, folate metabolism and methylation

  • MTHFR stands for methylenetetrahydrofolate reductase.
  • MTHFR is an enzyme involved in folate metabolism.
  • If there is not enough MTHFR, your body cannot break down enough folate.
  • Some folate broken down by your body is used to methylate DNA.
  • DNA methylation is one of the ways your body regulates which genes are turned on and off.
  • A single nucleotide polymorphism (SNP) is a mutation in DNA sequence at one place.
  • SNPs are very common.
  • There are multiple known SNPs that can occur in the MTHFR gene.
  • The two SNPs of interest in the MTHFR gene are called C677T and A1298C.
  • C677T mutation is found in 10% of North Americans, most commonly Hispanics and those of Mediterranean descent.
  • Having two copies of the C677T (called “being homozygous”) can cause mild MTHFR deficiency and result in too much homocysteine.
  • Increased homocysteine has been studied in connection to many conditions but the results are inconclusive.
  • A1298C mutation is not known to elevate homocysteine.
  • A1298C mutation may cause deficiency of BH4, which is important in neurotransmission and formation of nitric oxide.
  • There is no strong support in peer reviewed literature for the association of C677T or A1298C with disease. Many studies contradict each other.
  • There is no known link between MTHFR mutations and mast cell disease.

DNA methylation: How it works

  • DNA methylation is one of the ways your body controls which genes are turned on and off.
  • Methylation is important in cancer.
  • Methylation of tumor suppressor genes causes them to be turned off, resulting in cancers.

Mast cells, heparin and bradykinin: the effects of mast cells on the kinin-kallikrein system

  • The kinin-kallikrein system is a group of hormones that affect inflammation, blood pressure, coagulation and pain perception.
  • It also affects the cardiovascular system, including cardiac failure.
  • This system produces bradykinin.
  • Bradykinin has many functions, including GI contraction, bronchoconstriction, induction of cell proliferation, collagen synthesis and release of many molecules.
  • Bradykinin causes blood vessels to dilate, decreasing blood pressure.
  • Bradykinin affects sodium excretion from the kidneys, further decreasing blood pressure.
  • Bradykinin opposes the action of angiotensin II, which increases blood pressure.
  • Mast cells release bradykinin and molecules to make it.
  • Mast cells also release heparin, which can initiate bradykinin formation.
  • Too much bradykinin causes angioedema.
  • Mast cell degranulation occurs with physical trauma in part due to formation of bradykinin.
  • Bradykinin induces release of histamine, serotonin and other molecules.

Biphasic anaphylaxis

  • Monophasic anaphylaxis is one episode of anaphylaxis symptoms.
  • Biphasic anaphylaxis is a second episode of anaphylaxis symptoms after resolution of symptoms.
  • Late onset anaphylaxis occurs several hours after exposure to trigger.
  • Protracted anaphylaxis is a long episode of anaphylaxis symptoms despite treatment.
  • Higher doses of corticosteroids may decrease incidence of second phase.
  • Studies on frequency of biphasic anaphylaxis differ on rate of incidence, but most report around 20% of patients have biphasic anaphylaxis.
  • Second phase can occur over a day after the first.
  • Biphasic patients had longer lasting initial anaphylaxis reactions.
  • Biphasic patients statistically receive less epinephrine for the initial reaction, which may result in the second reaction.
  • Delay in administration of epinephrine, inadequate dosing of epinephrine and need for large doses of epinephrine make biphasic anaphylaxis more likely.
  • Previous cardiovascular history, older age and use of beta blockers are risk factors for biphasic reactions.
  • Oral ingestion of trigger makes biphasic reactions more likely.
  • Not clear if mastocytosis patients are more likely to experience biphasic reactions.

MCAS: Respiratory symptoms

  • Throat symptoms are common in MCAS.
  • MCAS reactions can cause inability to swallow or breathe due to angioedema.
  • Breathing difficulty requires epinephrine.
  • Low level difficulty of breathing (feeling like you can’t get a deep breath) is the most common MCAS respiratory symptom.
  • Chest x-ray and pulmonary function testing are usually normal in MCAS patients.
  • Prostaglandin D2 is a potent bronchoconstrictor.
  • Allergic asthma is not uncommon in MCAS.

Fragrance allergy

  • Inhalation can cause anaphylaxis.
  • There have been cases of patients who can ingest a food but react to inhalation, such as Baker’s asthma.
  • Fragrance is one of the top five allergens in North American and European countries.
  • Fragrance allergy can cause skin, eye and respiratory problems.
  • Perfume can cause asthma and other respiratory problems through an unclear mechanism.
  • A significant portion of the population reacts adversely to scented products, even when worn by others.
  • 5% of general population found scented products on others to be irritating.
  • 19% had symptoms from exposure to air fresheners.
  • 9% had symptoms from exposure to scented laundry products.
  • Essential oils can cause allergic reactions regardless of the purity.
  • Some essential oils have been tied to severe allergic reactions, such as clove oil.
  • Oils of citrus fruits liberate histamine and cause mast cell symptoms.
  • In mast cell patients, scents can cause severe full body reactions that are potentially life threatening or fatal.

MCAS: Pain

  • MCAS patients may experience many types of pain.
  • Bone pain, osteopenia and osteoporosis are common in MCAS.
  • Joints and soft tissues are often painful.
  • Mast cells are involved in chronic lower back pain and complex regional pain syndrome.
  • Serotonin can amplify pain signals in chronic pain.
  • Increased serotonin and mast cell counts are found in some patients with chronic abdominal pain.
  • 95% of body serotonin is found in the peritoneal cavity.
  • Tricyclic antidepressants inhibit serotonin release and are sometimes used for abdominal pain.