Chronic urticaria and angioedema: Part 1

Urticaria is the medical term for what we commonly call hives. It is often caused by an allergic process, but can occur for other reasons. Angioedema is swelling affecting the dermis, subcutaneous tissue, mucosa and submucosal tissues. Angioedema can be dangerous, particularly when the airway is obstructed by swelling.

Notably, the two conditions are closely related and are distinguished by the tissues affected. Urticaria is affects only the upper dermis. In this way, angioedema is sometimes considered a form of “inside hives”. These symptoms can occur as a result of allergy but also occur for other reasons.

Urticaria and angioedema are considered acute if they last for less than six weeks and chronic if they last for six weeks or more. Acute urticaria and angioedema are most often, but not always, the result of mast cell and basophil activation by both IgE and non-IgE mechanisms. Activation by complement fragments, antibody binding complexes, cytokines and blood pressure changes can contribute. Importantly, acute urticaria and angioedema usually have an obvious trigger and resolve on their own. Antihistamines and brief courses of steroids are generally used to manage symptoms.

Chronic urticaria usually does not an identifiable cause. The duration of CU (chronic urticaria and angioedema) varies, but physical urticarias are more likely to be long lasting. It is thought that CU affects 0.5-5% of the population. CU patients can have urticaria and angioedema, either alone or together. In these patients, cutaneous mast cells are the driving force and histamine is the most important mediator in these processes.

When biopsied, CU lesions often reveal infiltrates of lymphocytes, but sometimes other cells are present in infiltrates. In CU patients, the clotting cascade is sometimes activated, resulting in increased prothrombin fragments F1 and 2, and D-dimer. These have been suggested as markers of CU, but have not been verified.

CU is only rarely an IgE mediated reaction and is instead associated with a number of chronic conditions. Chronic infections like hepatitis B and C, EBV, HSV, helminthic parasites and H. pylori have been found to cause CU. Complement deficiencies, cryoglobulinemia, serum sickness, connective tissue disease, lupus, rheumatoid arthritis, thyroid disease (both hypo- and hyper-), neoplasms (such as SM), endocrine disorders and use of oral contraceptives are all linked to CU.

Autoimmune diseases are so frequently associated with CU that these patients are subclassified as having autoantibody associated urticaria. Autoantibody associated urticaria and angioedema, linked to thyroid antibodies, anti-IgE antibodies and anti-IgE receptor antibodies, is a subset of chronic idiopathic urticaria. Lupus, dermatomyositis, polymyositis, Sjogren’s and Still’s disease are all associated with CU. Celiac disease has been linked as well.

30-50% of CU patients make IgG antibodies to the IgE receptor and 5-10% make IgG to the IgE molecule. This often does not correlate with skin tests with the patient’s own serum or plasma (ASST, APST) and these tests are not known to affect treatment or identify a specific subgroup of patients. The importance of these IgG antibodies is not clear. Some consider these patients to be more severe, but it is not yet fully understood.

 

References:

Jonathan A. Bernstein, et al. The diagnosis and management of acute and chronic urticaria: 2014 update. J Allergy Clin Immunol Volume 133, Number 5.

Usmani N,Wilkinson SM. Allergic skin disease: investigation of both immediate and delayed-type hypersensitivity is essential. Clin Exp Allergy 2007;37:1541-6.

Zuberbier T, Maurer M. Urticaria: current opinions about etiology, diagnosis and therapy. Acta Derm Venereol 2007;87:196-205.

I am rare

A year ago this week, I started writing regular posts about mast cell disease and chronic illness. In honor of Rare Disease Day, the last day of February, I decided to put up short posts on Facebook daily for the remaining days of February. I could not have predicted that this would eventually give way to a website that is visited thousands of times a month by people all over the world.

I wanted to write a post about having a rare disease and what it meant to be a rare patient, but I have actually been too busy dealing with my rare disease to do it. This week, it occurred to me that I actually have multiple rare diseases. Today, I learned that four of my diagnoses are classified as rare diseases in the US. I have four individual rare diseases. This is not uncommon for mast cell patients.

In the US, any disease that affects less than 200,000 at one time is considered rare. These diseases can be infectious diseases, cancers, genetic disorders, autoimmune diseases, and so on. Rare diseases are defined differently by different countries and organizations. Likewise, a disease can be rare in one region and common in another.

There are over 7000 known rare diseases. Worldwide, they affect 300,000,000 people. In the US, they affect 25,000,000. If all rare diseases live together in one country, it would be the third most populous country in the world.

Almost 10% of the American population has at least one rare disease. 2/3 of Americans living with rare disease are children. Currently, only 350 rare diseases have an FDA approved treatment. This means that most of the medications we use are not designed for us and we don’t know how they will affect us.

Almost half of primary care physicians in the US say they feel uncomfortable with taking on a rare disease patient. It can take us up to six years to receive a correct diagnosis. Some people are never diagnosed.

80% of rare disease patients have one of 350 rare diseases, with the rest being significantly more rare. Mastocytosis is not one of those 350 diseases.

 

My name is Lisa Klimas. I am 31 years old and I live with four rare diseases.

Mast cell disease causes severe allergic reactions to things I am not actually allergic to.

Ehlers Danlos Syndrome causes hernias, joint instability, and poor wound healing.

Postural Orthostatic Tachycardia Syndrome causes dysregulation of blood pressure and heart rate.

Mixed connective tissue disease causes autoimmune activity against various tissues in my body.

All of these conditions are chronic, incurable, and painful.  Together they can cause life threatening complications.

February 28th is Rare Disease Day. For many people, it is just another day. But for me, it is a celebration.

It is a reminder that there are other people like me all over the world.

Alone, we are rare, but together we are many.  We are strong.  We are an army.

My name is Lisa Klimas and I am rare.

 

I am rare

 

 

 

*All figures from the National Organization for Rare Disorders (NORD).