June 2015: Post summaries and take home points

Mast cells in wound healing
• When a wound occurs, the complement system is activated to form a clot.
• Complement molecules activate mast cells and induce degranulation.
• Mast cells work to prevent excessive clotting.
• Mast cells break down the extracellular matrix to make room for new cells to close the wound.
• Mast cells drive generation of new blood vessels.
• Histamine and tryptase mediate formation of new muscles.
Angioedema: Part 1
• Hereditary angioedema (HAE) is a heritable blood disorder that causes episodes of protracted swelling that can be life threatening.
• Angioedema is when fluid leaves the bloodstream and gets trapped between the deep dermis and subcutaneous tissue.
• Swells can last up to five days.
• About 30% of HAE patients get a pink ring rash.
• HAE patients do not have hives or itching.
• Swelling can affect any part of the body.
• Swelling of the tongue and throat can cause suffocation.
• Abdominal swells are often misinterpreted as “acute abdomen” requiring surgery.
• 85% of patients have type I.
• 15% have type II.
• Type III cases are rare.
• All three are treated similarly.
• Bradykinin causes blood vessels to dilate, decreasing blood pressure and causing fluid to become trapped in tissues.
• C1 inhibitor (C1INH) regulates the C1 protein, which activates the complement system (for fighting infections), controls formation of blood clots and generation of bradykinin.
Angioedema: Part 2
• In HAE type I, C1 inhibitor (C1INH), C4 and C2 levels are low; C1q is normal.
• In HAE type II, C1INH is normal or a little increased, C4 and C2 are low, C1q is normal; C1INH functions poorly.
• In HAE type III, C1INH is normal and functional; C4 may be normal.
• HAE attacks can cause airway constriction leading to suffocation.
• More than half of HAE patients will experience this type of swelling at least once.
• Swells usually last 2-3 days and then resolve.
• Antihistamines and steroids do not resolve this type of swelling.
• HAE has many triggers in common with mast cell disease, including foods, estrogen level, psychological stress and physical triggers.
• Cinryze, Berinert and Ruconest are C1INH solutions for IV use.
• Kalbitor is a kallikrein inhibitor for SQ injection.
• Firazyr is a bradykinin receptor blocker for injection.
• Medications like danazol and tranexamic acid are seeing less use with several new meds available.
Angioedema: Part 3
• Acquired angioedema (AAE) patients have deficiency of C1 esterase inhibitor (C1INH) that is not due to genetic defect.
• AAE is ten times less common than HAE.
• AAE often presents with low CH50, C2, C4 and sometimes C1q, poorly functioning or low C1 esterase inhibitor (C1INH).
• AAE can occur secondary to many autoimmune and hematologic diseases.
• Type I AAE has poor function of C1INH.
• Type II AAE has autoantibodies to C1INH.
• Idiopathic angioedema is three episodes of angioedema in 6-12 months without a clear reason.
• Type III HAE patients sometimes have mutations in the Factor XII gene, but not all.
• Type III patients have four attacks a year on average.
• Estrogen levels are more likely to induce angioedema in Type III patients than in other types of angioedema.
• Bruising and clotting issues are sometimes seen in type III HAE patients.
Angioedema: Part 4
• Deficiencies of complement molecules C1q, C1r, C1s, C2, C4 are associated with lupus like autoimmune conditions.
• Without these molecules, dead cells and debris cannot be removed and cause local inflammation.
• In HAE types I and II, complement molecules C2 and C4 are low.
• Deficiency in C2 and C4 might predispose to autoimmune disease.
• One study found 13.2% HAE patients had autoantibodies to thyroid.
• 47.5-48% of HAE patients had at least one autoantibody when tested with a panel for several autoantibodies.
• On average, 10% of the healthy population has at least one autoantibody.
• 12% of HAE patients had autoimmune disease when tested with a panel for several autoimmune conditions.
• HAE patients often have a decreased sense of smell.
• HAE patients have increased B cell activation and autoreactive B cells, which contributes to autoimmunity.
Activating the complement system: Classical, alternative and lectin pathways
• The complement system is many proteins that can circulate in the bloodstream.
• Other proteins can cut off pieces of these proteins to activate the proteins.
• Once the proteins are activated, they help kill infecting organisms.
• The classical pathway is activated by C1 protein when microbes are present.
• The alternative pathway is activated by the C3 protein changing into C3b.
• The lectin pathway is activated by two proteins called MBL and ficolin binding to the surfaces of microbes.
• These pathways release C3a and C5a, which activate mast cells.
• C1 inhibitor (C1INH) inactivates C1r and C1s to stop the complement pathway.
Deconditioning, orthostatic intolerance, exercise and chronic illness – Part 6
• Exercise can treat deconditioning due to orthostatic intolerance.
• Exercise can also exacerbate symptoms in deconditioned patients.
• It is worse when coupled with hot weather or eating before exercise.
• A sustained hand grip will raise blood pressure for a short time.
• Performing the hand grip when changing position or after exercising or eating can help mitigate OI symptoms.
• Leg crossing while tensing muscles can also help regulate blood pressure before standing.
• Multiple studies have demonstrated that regular exercise can help manage POTS.
• Recumbent exercise is helpful when starting to work out as it is less likely to trigger OI symptoms.
• Some patients are able to recover significant capability and are able to engage in athletic activities.
• Exercise for chronic fatigue and fibromyalgia patients has also had success in improving deconditioning symptoms and quality of life.
Deconditioning, orthostatic intolerance, exercise and chronic illness – Part 7
• Volume expansion (use of IV hydration or volume expander like dextran) can improve symptoms in deconditioned patients.
• Volume expansion does not improve exercise capacity.
• IV saline with exercise gives the best results for symptom relief.
• Volume expansion can mitigate the effect of heat stress on the body.
• Volume expansion alone stabilized blood supply to the head.
• 86% of POTS patients in a study reported IV saline as the best treatment for brain fog.
• Mast cell degranulation can cause hypotension and vasodilation.
• Mast cell mediator release can cause fluid loss from blood resulting in edema.
• Volume loading in the form of IV fluids may decrease mast cell symptoms due to deconditioning, orthostatic intolerance and capillary leakage.

1 Response

  1. Yvonne Marcoux August 14, 2015 / 12:59 pm

    Thanks again for all your hard work putting together this important information. I believe my Mom has MCAS but is unable to get the necessary testing for diagnosis. She has (recently) unexplained bouts of angioedema. This mostly affects her breathing and is visible in her limbs. She responds well to lasix (flurosemide) and gets better. The difficulty is in convincing the doctors that she does not have pneumonia (upon which they perscribe heavy antibiotics which cause more attacks). She is facing kidney failure and has chosen to pass away.
    We thank you very much and I have used the emergency protocols you have forwarded and gave me the confidence to speak up and try to help her the best I could. So you have helped me save her life a number of times and she got a last visit with her son, daughter in law and 2 young grandchildren who live far away.
    I know that MCAS is real and thank you for your voice. It has helped me to find mine.
    Thank you so very much,

    Yvonne Marcoux

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