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 ?:
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
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1:
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Bedbug bites masquerading as urticaria.J Allergy Clin Immunol. 2006 Jun;117(6):1508-9.
No abstract available. |
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2:
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Yasnowsky KM, Dreskin SC, Efaw B, Schoen D, Vedanthan PK,
Alam R, Harbeck RJ. |
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Chronic urticaria sera increase basophil CD203c expression. |
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3:
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Successful treatment of
cold-induced urticaria/anaphylaxis with anti-IgE. |
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4:
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Levocetirizine : a review of
its use in the management of allergic rhinitis and skin allergies. |
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5:
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Quality of life in patients with
urticaria. |
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6:
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Chronic urticaria:
pathophysiology and etiology, or the what and why. |
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7:
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Oral anticoagulants may prevent
NSAID-induced urticaria. |
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8:
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Ujiie H, Shimizu T, Natsuga
K, Arita K, Tomizawa K,
Shimizu H. |
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Severe cholinergic urticaria
successfully treated with scopolamine butylbromide
in addition to antihistamines. |
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9:
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Diagnosis of delayed pressure
urticaria. |
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10:
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Annesi-Maesano I, Beyer A, Marmouz
F, Mathelier-Fusade P, Vervloet
D, Bauchau V. |
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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. |
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11:
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Gonzalez de Olano
D, Roan Roan J, de la Hoz Caballer B, Cuevas Agustin M, Hinojosa Macias M. |
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Urticaria induced by
antihistamines. |
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12:
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El-Qutob
Lopez D, Morales Rubio C, Cervera Aznar R, Pelaez Hernandez A. |
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Allergic reaction after
ingestion of orange blossom pollen. |
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13:
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Is there a role for antileukotrienes in urticaria? |
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14:
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Montelukast treatment of urticaria. |
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15:
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Levocetirizine is an effective treatment in patients suffering from
chronic idiopathic urticaria: a randomized, double-blind, placebo-controlled,
parallel, multicenter study. |
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16:
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Urticaria and lip fasciculation
may be prodromal signs of brain malignancy. |
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17:
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Chronic urticaria due to Blastocystis hominis. |
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18:
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Chronic idiopathic urticaria
with functional autoantibodies: 12 years on. |
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19:
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Emerging drugs for chronic
urticaria. |
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20:
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Levocetirizine in patients with chronic idiopathic urticaria: results
of a multicenter clinical practice study. |
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21:
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Chronic urticaria: a cutaneous manifestation of celiac disease. |
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22:
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