URTICARIA AND ANGIOEDEMA                     

Bob Lanier M.D.  (Version 6.15.06)

 

EXECUTIVE SUMMARY: ( a more in-depth work follows below)

When you get through reading this – if you are a new patient – please click here to go through the questions we need to know

 

Background

 

If normal body chemicals (mostly HISTAMINE) are released superficially in the skin, there is itching and hives which look like insect bites at first..   The location of the hives is usually not helpful in the diagnosis unless it is beneath a pressure area like a beltline or sock line.  If the histamine is released in deeper tissue, it usually burns more than itches and affects loose tissue such as the lips and eyelids. Called angioedemia, it is the same basic process as the more typical hives.  First time urticaria usually lasts less than 4-6 weeks.   It may affect 15-20% of the general population with the woman 35-60  being more common in the recurrent form.  

Why it happens

Think of histamine release in much the same way as you would the common symptom of “fever”.   Fever is not a disease, but rather a symptom or a “signal” of high immune activity.   Releasing histamine is the immune system’s way of attracting your attention ( works eh?).   If the signal is meaningful and reflects major organ problems ( liver, thyroid, infection) we uniformly  diagnose it.  If the signal is weak we may not often identify the cause.   If we don’t find a real cause, the symptoms tend to go away on their own ( viral, hormones causes do this) while we cover the symptoms with antihistamines.  If we do find a cause, we will treat the root of the problem.

How we work it up:

After a review of your history ( provided in part by the questionnaire at the end of this summary), a physical exam is completed.   I will be looking for any evidence of even minor infections ( even toenail fungus – tell me). I will also do a limited amount of skin testing for allergy.  Also a small blood sample will be drawn for common medical problems known associated with urticaria.

What you need to do:

Spend time on the questionnaire below – take antihistamines very regularly – even when the hives are not present.

URTICARIA: in more depth

When you get through reading this – if you are a new patient – please click here to go through the questions we need to know

( note: the vast majority of this review is extracted from the Medical Clinics of North America May 2004, Volume 24, Number 2, edited by Stephen Dreskin and books edited by Drs. Kaplan and Wanderer, the generally recognized world experts.   Other literature sources including articles in common medical journals will be included in the bibliography at the end)

BASIC PRINCIPLE:  LIKE OTHER BODY MESSENGER SYSTEMS INCLUDING FEVER, THIS IS A SYMPTOM – NOT A DISEASE.   LESS THAN 50% OF URTICARIA HAS AN IDENTIFIABLE CAUSE.

BACKGROUND AND OVERVIEW:

The name urticaria comes from the name of the stinging nettle plant ( Latin, urtica).  Urticaria was mentioned by the Chinese in the 7th century, then best described by the Englishman James Heberden in 1772 :  “The little elevations upon the skin in the ‘nettle rash’ often appear involuntarily, especially if the skin be rubbed, or scrubbed, and seldom stay many hours in the same place, and sometimes not many minutes. There is no body (part) exempt from “them” and by far the greatest experience no other evil from it besides the intolerable anguish from the itching..”   Hives is the more common term used now,

ARE YOU SURE IT IS HIVES ?:

Text Box:    The areas are raised, may be pink or red – or in some cases pale surrounded by a pink flare. They may start as round, from pinpoint to a quarter of an inch – expanding into another to form large wheals. The wheals come and go – sometimes in minutes, sometimes in several hours.  Areas that are painful, last more than 24 hours, leave pigmentary change, form blisters, or look like bruises may suggest another process and should be seen by a dermatologist.

HOW MANY PEOPLE SUFFER:

Studies show that 15-25% of the population experience this irritation problem at least once in their lifetime, with women between the age of 30 – 50 years being most commonly affected.  Over a million doctor visits are made each year – you are not alone.   Over half of people with hives also have swelling called angioedemia.

Of people with urticaria, 60% have the recurrent variety, 5% have the vasculitic type and 35% have a physical urticaria.

HOW BAD IS IT?

While many people with this problem complain that other people, even doctors, are less than sympathetic, careful surveys reveal that patients with ongoing urticaria have an equally poor quality of life as people with severe heart disease awaiting bypass surgery.   Of 745 medical problems ranked by doctors in priority, ongoing urticaria was listed as 684th – unworthy of funding ( Oregon Health Plan).   This problem is  clearly insignificant – unless you have it personally.  

HOW LONG WILL IT LAST?

The prognosis for chronic urticaria is pretty good – it does pass, and most people erroneously feel whatever they were doing last is the reason they are better ( diets, exercise, stress reduction).  50% of people are free I a year, another 20% of people in 5 years – but 10-20% of people battle this for 10-20 years.   Most of the long term folks also have swelling ( angioedemia) – that’s a marker. 

WHO SHOULD YOU SEE ?

This problem is equally frustrating to all specialties as a multi-disciplinary issue.  Primary care doctors see the bulk of patients (59%), dermatologists see 21%, allergists see12 %.   If the spots come and STAY as opposed to coming and GOING- you need to see a dermatologist since there may be a skin biopsy indicated.   If the spots and swelling come and go, the choice could include allergist.

DIAGNOSE THIS YOURSELF ?     DIFFERENTIAL DIAGNOSIS AND CLASSIFICATION

HOW TO START

The best way to identify a specific inciting material is you to provide the most accurate history possible.   To that end there will be at the end of this summary a detailed questionnaire for you to fill out.

The basic classification is “Acute” and “Chronic”.   Acute urticaria is first time hives lasting six weeks or less.  Chronic urticaria lasts more than six weeks and may be intermittent.  While there are many classifications, I will break them down mostly into Common, Physical, and Idiopathic ( meaning we have no clue).

1. COMMON URTICARIA-  the majority of problems are in this area, produced by autoimmune antibodies, or infection, or an unknown mechanism. 

A. Associated diseases: It is also known that certain disease problems are commonly associated with urticaria including thyroid disease where the thyroid is either under active or overactive.   In some studies, anti-thyroid antibodies are commonly found in urticaria patients even when the usual thyroid tests are normal.

B. Infections: particularly are viral disease thought to be among the most common causes for acute urticaria.   In allergic people, a sinus infection or either viral or bacteria nature is sometimes accompanied by urticaria.  Dental infections, prostatitis, and abscesses may be a cause.  Chronic urticaria is sometimes associated with parasites ( malaria, giardia, amoeba).   Seemingly insignificant infections like toenail fungus, athletes foot, and the organism thought responsible for stomach ulcers ( h pylori) have been suggested.

C. Cancer- unlikely to be the cause – but sometimes seen in cancer stressed individuals

D. Foods and supplements:  Immediate food sensitivities are the easiest because the cause and effect are so clear cut.  “I eat a peanut - I break out”   The most common food allergy producing this will be peanuts, egg, milk, wheat corns, shrimp, orange, cranberry, garlic, and ginger.  Food allergy, while usually the biggest concern of most patients,  is a very small portion of urticaria.

Foods which produce non-allergic issues include eating fish with high histamine content ( Scromboid poisoning) – you will not likely be exposed to this unless you are a scuba diver, or visitor to an island off a reef.

 More common and harder to notice may involve “over the counter” , prescription , additives, supplements or herbal remedies.     These compounds have been reported to produce problems. Herbs, feverfew, willow, glucasamine, horseradish, hypericum, phyoestrogen, propolis, royal jelly, and valerian among others.

            E, Drugs-  While drugs may involved, the reaction may not be “allergic” in the usual sense – that is, skin tests are generally negative.  A very common problem is aspirin and NSAIDs (Motrin, Advil, Alieve).   Tylenol is NOT generally an issue. Blood pressure drugs like ACE INHIBITORS not only have a frequent side effect of cough, but also have a relatively high association with hives. Beta blockers are blood pressure drugs also, and are associated with urticaria ( they may also be found in eye drops for glaucoma)..  Other less common drugs include codeine or opiates, vancomycin, and the dye used in x-ray procedures.  

( When you get through reading this – if you are a new patient – please click here to go through the questions we need to know

 

2. PHYSICAL URTICARIA:  these may be more persistent and less responsive to treatment than the others.  

            A. Aquagenic: perhaps associated with cold urticaria, the most common presentation is the development of urticaria with a shower or by jumping into a swimming pool

            B. Cholinergic:  Marked by small wheal with large area of redness, usually following exertion – the itching is very intense and may be related to the sweating reflex.  Spicy foods and emotional distress are sometimes associated with this type.

C. Exercise induced- a variant of cholinergic urticaria

D. Cold Urticaria: This is sometimes hereditary, and be noticed particularly by people handling ice.   A common test is to apply an ice cube to the forearm for two minutes, then note the emergence of a wheal.

E. Delayed pressure: this is sometimes seen following a heavy pressure ( an unpadded strap on a heavy bag etc) by several hours. The symptoms are not usually that itchy and are more likely to involve swelling ( angioedemia).

F. Vibratory urticaria and angioedemia:  A variant of delayed pressure urticaria may be seen in jackhammer workers or in lab workers using shakers to mix fluids.

G. Dermatographism: People with this type may not see physicians as often, but remark that if they scratch have whelps arise.  If you can stoke your skin with a paper clip and see the effect in a whelp, you have a physical urticaria.

I. Solar Urticaria- some people break out on in sun exposed areas – that could the sunscreen they are using, the effects of an antibiotic in association with the sun, or unknown mechanisms

J. Contact urticaria: Craft soaps ( “home made” soaps) with special aromas, fragrances, and colors are being reported more often.  All ointments and creams should be evaluated. Herbal materials may also contain neomycin, nickel, thimerosol are common contact sensitivies as is Latex.

Urticaria Vasculitis: a more serious problem, it is important to know if the itchy wheals come and go – or come and stay in one day.   Wheals that stay may justify a biopsy from a dermatologist looking for a more extensive process called vasculitis.

Angioedemia: the same basic process as hives except that the histamine release is deeper in the tissues.   Just before swelling of the lips or eyes, people note a burning sensation, then an appalling and sometimes temporarily disfiguring swelling. It passes within a few hours for most.   While there is a more significant problems associated with swelling of a hereditary nature – it is rare.

CLINICAL AND LABORATORY EVALUATION

The laboratory work-up ( blood work) of this condition is very commonly negative with the exception of thyroid assays.  About 14% of recurrent urticaria patients have evidence of thyroid antibodies, and sometimes….. sometimes… respond to thyroid supplementation.  Evaluation should include ESR ( Erythrocyte sedimentation rate) or CRP ( C reactive protein), antihyroid antibodies ( antithyroglobulin / antithyroid peroxisomal antibodies ), thyroid function,  ANA ( for lupus) CBC with differential, and if the problem is persistent – a skin biopsy. On occasion, the lab work will include tests looking for hepatitis.

Allergy testing: while a few skin tests may be helpful to establish the presence of allergy, extended tests especially large panels of food tests are not usually helpful at all since most people can readily tell the doctor which food is at issue ( the cause and effect being so closely associated). If foods are suspected, a dietary effort should prove diagnostic.  

On occasion, a controversial skin test (ASST – autologous serum skin test) t using the patient’s own serum ( the clear part of the red blood mixture)is done.   A positive result may indicate the patient has an auto-antibody.  The significance resides in the justification for more aggressive treatment including steroids and other immunosuppressive drugs. A positive ASST result is commonly NOT seen in vasculitis 

(When you get through reading this – if you are a new patient – please click here to go through the questions we need to know)

TREATMENT

H1 antihistamines

            Zyrtec 10 mg up to two tablets three times a day

            Allegra 180 mgm 1-3 tablets twice a day

            Older antihistamines to tolerance

The foundation for treatment ( since the problem is the release of histamine) is  antihistamines.   They come in two flavors called H1 and H2.   The H1 antihistamines are the most commonly used for both urticaria and angioedemia as well as the more common allergy symptoms for the nose.   Examples are the older sedating medicines like Benadryl, as well as the newer antihistamines that don’t make you sleepy like Allegra, Clarinex, and Zyrtec. The doses required, however, may exceed usual doses by quite a bit.

H2 antihistamines

The H2 antihistamines are more commonly used for stomach problems and are best recognized as over the counter Zantac or Tagamet.  These medications are marginally useful since the receptor they work on is only about 15% of the total receptors in the skin ( the 85% being the H1 type).

 A very very potent combination H1 and H2 antihistamine (Doxepin) is more commonly used as an antidepressant.  It is thought to be 800 times more potent than Benadryl and six times more potent than Zantac.  The doses used for urticaria are much less than that used for depression – but even so, the side effects of sedation are significant, and reports of weight gain discourage much use by women.

Singular – an agent sometimes used for the management of asthma has some reported success in the treatment of urticaria.

Steroids- oral steroids are useful to break and allergic cycle and are occasionally used in more chronic  fashion.   There are significant side effects if used for long periods or high doses, but skilled physicians can use them in combination with antihistamines to improve the quality of life.

Methyl trexate  - a very potent and very serious drug - 7.5 mgm first week, then 15 25 mgm weekly + HAVE TO HAVE  folic acid 1mgm 6days a week, monthly blood count, liver functions.   Side effects may include transient hair loss

Cyclosporine  a very potent and very serious drug - 2.5-4.0mgm/kg/day – very good response rate.   Side effects include renal dysfunction, high blood pressure.

Other reported treatments for the most severe of cases include Intravenous gammaglobulin, Acyclovir , interferon, plasmapheresis and Dapsone.

THE FUTURE OF TREATMENT

Autoimmune: An Immune globulin G antibody against the allergic antibody ( IgG vs. anti-IgE or IgG against the FC epsilon R1a receptor – sorry – more information than you wanted )  is thought to be the most common reason for common urticaria of a non-allergic nature.  Unfortunately there are no commercial laboratory tests available for this.

There are some studies starting using monoclonal anti-IgE ( Xolair ).   It is a very safe compound, but extremely expensive and usually not covered by health insurance.

 

When you get through reading this – if you are a new patient – please click here to go through the questions we need to know

 

Here is recent search of the medical literature: you can spend the day at the medical library and work on this issue yourself

1:

Scarupa MD, Economides A.

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No abstract

Bedbug bites masquerading as urticaria.J Allergy Clin Immunol. 2006 Jun;117(6):1508-9. No abstract available.
 

 

2:

Yasnowsky KM, Dreskin SC, Efaw B, Schoen D, Vedanthan PK, Alam R, Harbeck RJ.

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Abstract

Chronic urticaria sera increase basophil CD203c expression.
J Allergy Clin Immunol. 2006 Jun;117(6):1430-4. Epub 2006 Apr 27.
 

 

3:

Boyce JA.

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Abstract

Successful treatment of cold-induced urticaria/anaphylaxis with anti-IgE.
J Allergy Clin Immunol. 2006 Jun;117(6):1415-8. Epub 2006 May 11.
 

 

4:

Hair PI, Scott LJ.

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Abstract

Levocetirizine : a review of its use in the management of allergic rhinitis and skin allergies.
Drugs. 2006;66(7):973-96.
 

 

5:

Weldon DR.

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Abstract

Quality of life in patients with urticaria.
Allergy Asthma Proc. 2006 Mar-Apr;27(2):96-9.
 

 

6:

Schocket AL.

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Abstract

Chronic urticaria: pathophysiology and etiology, or the what and why.
Allergy Asthma Proc. 2006 Mar-Apr;27(2):90-5.
 

 

7:

Asero R.

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No abstract

Oral anticoagulants may prevent NSAID-induced urticaria.
Clin Exp Dermatol. 2006 Jun;31(4):589-90. No abstract available.
PMID: 16716169 [PubMed - in process]

 

8:

Ujiie H, Shimizu T, Natsuga K, Arita K, Tomizawa K, Shimizu H.

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No abstract

Severe cholinergic urticaria successfully treated with scopolamine butylbromide in addition to antihistamines.
Clin Exp Dermatol. 2006 Jun;31(4):588-9. No abstract available.
PMID: 16716168 [PubMed - in process]

 

9:

Godse KV.

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Free Full Text

Diagnosis of delayed pressure urticaria.
Indian J Dermatol Venereol Leprol. 2006 Mar-Apr;72(2):155-6. No abstract available.
PMID: 16707829 [PubMed - in process]

 

10:

Annesi-Maesano I, Beyer A, Marmouz F, Mathelier-Fusade P, Vervloet D, Bauchau V.

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Abstract

Do patients with skin allergies have higher levels of anxiety than patients with allergic respiratory diseases? Results of a large-scale cross-sectional study in a French population.
Br J Dermatol. 2006 Jun;154(6):1128-36.
PMID: 16704645 [PubMed - in process]

 

11:

Gonzalez de Olano D, Roan Roan J, de la Hoz Caballer B, Cuevas Agustin M, Hinojosa Macias M.

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Free Full Text

Urticaria induced by antihistamines.
J Investig Allergol Clin Immunol. 2006;16(2):144-6.
PMID: 16689192 [PubMed - in process]

 

12:

El-Qutob Lopez D, Morales Rubio C, Cervera Aznar R, Pelaez Hernandez A.

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Free Full Text

Allergic reaction after ingestion of orange blossom pollen.
J Investig Allergol Clin Immunol. 2006;16(2):140-1.
PMID: 16689190 [PubMed - in process]

 

13:

Di Lorenzo G, Pacor ML, Mansueto P, Esposito-Pellitteri M, Ditta V, Lo Bianco C, Leto-Barone MS, Di Fede G, Rini GB.

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Abstract

Is there a role for antileukotrienes in urticaria?
Clin Exp Dermatol. 2006 May;31(3):327-34.
PMID: 16681569 [PubMed - in process]

 

14:

McBayne TO, Siddall OM.

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Abstract

Montelukast treatment of urticaria.
Ann Pharmacother. 2006 May;40(5):939-42. Epub 2006 May 2.
PMID: 16670370 [PubMed - in process]

 

15:

Kapp A, Pichler WJ.

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Abstract

Levocetirizine is an effective treatment in patients suffering from chronic idiopathic urticaria: a randomized, double-blind, placebo-controlled, parallel, multicenter study.
Int J Dermatol. 2006 Apr;45(4):469-74.
PMID: 16650180 [PubMed - in process]

 

16:

Shamsadini S, Varesvazirian M, Shamsadini A.

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Free Full Text

Urticaria and lip fasciculation may be prodromal signs of brain malignancy.
Dermatol Online J. 2006 Mar 30;12(3):23.
PMID: 16638437 [PubMed - in process]

 

17:

Gupta R, Parsi K.

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Abstract

Chronic urticaria due to Blastocystis hominis.
Australas J Dermatol. 2006 May;47(2):117-9.
PMID: 16637808 [PubMed - in process]

 

18:

Sabroe RA, Greaves MW.

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Abstract

Chronic idiopathic urticaria with functional autoantibodies: 12 years on.
Br J Dermatol. 2006 May;154(5):813-9.
PMID: 16634880 [PubMed - in process]

 

19:

Asero R, Tedeschi A.

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Abstract

Emerging drugs for chronic urticaria.
Expert Opin Emerg Drugs. 2006 May;11(2):265-74.
PMID: 16634701 [PubMed - in process]

 

20:

Pfaar O, Wrede H, Barth C, Hansen I, Klimek L.

Related Articles, Links

No abstract

Levocetirizine in patients with chronic idiopathic urticaria: results of a multicenter clinical practice study.
Int J Clin Pharmacol Ther. 2006 Apr;44(4):191-2. No abstract available.
PMID: 16625989 [PubMed - indexed for MEDLINE]

21:

Haussmann J, Sekar A.

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Abstract

Chronic urticaria: a cutaneous manifestation of celiac disease.
Can J Gastroenterol. 2006 Apr;20(4):291-3.
PMID: 16609761 [PubMed - in process]

 

22:

Wananukul S, Chatchatee P, Chatproedprai S.

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