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. If you have not already done so: – please click here to go
through the questions we need to know
URTICARIA: in more depth
( 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.
HERES WHAT WE ARE LOOKING FOR AND HOW WE LOOK FOR IT IN TABLES:
|
Chronic
Urticaria Data This approach is designed to screen for the most
associated neoplasia, mastocystosis, occult inflammation, complement
disorders, Autoimmune disease and allergy
with the process of chronic idiopathic urticara |
||
|
Hematology |
RBC |
|
|
|
WBC |
|
|
|
EOS |
|
|
|
Tryptase |
|
|
Inflammation |
ALT |
|
|
|
Sinus xr |
|
|
|
CRP |
|
|
Endocrine |
TSH |
|
|
Complement |
CH50 |
|
|
Allergic |
IgE |
|
|
|
RAST 0 |
|
|
|
RAST1 |
|
|
Autoimmune |
FcER1 Panel |
|
|
Complement |
CH50 |
|
|
Allergic |
IgE |
|
|
|
RAST 0 |
|
|
Physical |
ice cube |
|
|
Autoimmune |
FcER1 Panel |
|
The major causes of
urticaria and angioedema that should be considered when any patient is
being evaluated are as follows: 1.
Drug reactions 2.
Foods or food additives 3.
Inhalation, ingestion of, or contact
with antigens 4.
Transfusion reactions 5.
Infections: bacterial, fungal, viral,
and helminthic 6.
Insects (papular urticaria) 7.
Collagen vascular diseases a.
Cutaneous vasculitis b.
Serum sickness 8.
Malignancy: angioedema with acquired C1
and C1- inactivator (C1- INH) depletion 9.
Physical urticarias a.
Cold urticaria b.
Cholinergic urticaria c.
Dermographism d.
Pressure urticaria (angioedema) e.
Vibratory angioedema f.
Solar urticaria g.
Aquagenic urticaria 10.
Urticaria pigmentosa: systemic
mastocytosis 11.
Hereditary diseases a.
Hereditary angioedema b.
Familial cold urticaria c.
C3b inactivator deficiency d.
Amyloidosis with deafness and urticaria
12.
Chronic idiopathic urticaria and
chronic angioedema
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.
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
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.
Here is recent search of
the medical literature: you can spend the day at the medical library and work
on this issue yourself
Look forward to talking
with you
Bob Lanier MD
|
1: |
||
|
|
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. |
|
|
|
Chronic urticaria sera increase
basophil CD203c expression. |
|
|
3: |
||
|
|
Successful treatment of
cold-induced urticaria/anaphylaxis with anti-IgE. |
|
|
4: |
||
|
|
Levocetirizine : a review of its
use in the management of allergic rhinitis and skin allergies. |
|
|
5: |
||
|
|
Quality of life in patients with
urticaria. |
|
|
6: |
||
|
|
Chronic urticaria:
pathophysiology and etiology, or the what and why. |
|
|
7: |
||
|
|
Oral anticoagulants may prevent
NSAID-induced urticaria. |
|
|
8: |
Ujiie H, Shimizu T, Natsuga K, Arita K,
Tomizawa K, Shimizu H. |
|
|
|
Severe cholinergic urticaria
successfully treated with scopolamine butylbromide in addition to
antihistamines. |
|
|
9: |
||
|
|
Diagnosis of delayed pressure
urticaria. |
|
|
10: |
Annesi-Maesano I, Beyer A, Marmouz F,
Mathelier-Fusade P, Vervloet D, Bauchau V. |
|
|
|
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. |
|
|
11: |
Gonzalez de
Olano D, Roan Roan J, de la Hoz Caballer B, Cuevas Agustin M, Hinojosa Macias
M. |
|
|
|
Urticaria induced by
antihistamines. |
|
|
12: |
El-Qutob
Lopez D, Morales Rubio C, Cervera Aznar R, Pelaez Hernandez A. |
|
|
|
Allergic reaction after
ingestion of orange blossom pollen. |
|
|
13: |
||
|
|
Is there a role for
antileukotrienes in urticaria? |
|
|
14: |
||
|
|
Montelukast treatment of
urticaria. |
|
|
15: |
||
|
|
Levocetirizine is an effective
treatment in patients suffering from chronic idiopathic urticaria: a
randomized, double-blind, placebo-controlled, parallel, multicenter study. |
|
|
16: |
||
|
|
Urticaria and lip fasciculation
may be prodromal signs of brain malignancy. |
|
|
17: |
||
|
|
Chronic urticaria due to
Blastocystis hominis. |
|
|
18: |
||
|
|
Chronic idiopathic urticaria
with functional autoantibodies: 12 years on. |
|
|
19: |
||
|
|
Emerging drugs for chronic
urticaria. |
|
|
20: |
|||
|
|
Levocetirizine in patients with
chronic idiopathic urticaria: results of a multicenter clinical practice
study. |
||
|
21: |
|||
|
|
Chronic urticaria: a cutaneous
manifestation of celiac disease. |
||
|
22: |
||
|
|
Food induced urticaria in
children. |
|
|
23: |
Du Toit G, Prescott R, Lawrence P, Johar A,
Brown G, Weinberg EG, Motala C, Potter PC. |
|
|
|
Autoantibodies to the
high-affinity IgE receptor in children with chronic urticaria. |
|
|
Contact urticaria to Cannabis
sativa. |
||
|
Urticaria and quality of life. |
||
|
26: |
||
|
|
Occupational contact urticaria. |
|
|
27: |
||
|
|
Chronic urticaria and thyroid
auto-immunity. |
|
|
28: |
||
|
|
Urticaria and hepatitis. |
|
|
29: |
||
|
|
Drug-induced urticarias. |
|
|
30: |
||
|
|
Eosinophils and urticaria. |
|
|
31: |
Hennino A, Berard F, Guillot I, Saad N,
Rozieres A, Nicolas JF. |
|
|
|
Pathophysiology of urticaria. |
|
|
32: |
||
|
|
Somatization disorders in
dermatology. |
|
|
33: |
||
|
|
Angioedema from angiotensin-converting
enzyme (ACE) inhibitor treated with complement 1 (C1) inhibitor concentrate. |
|
|
34: |
||
|
|
Resolution of chronic urticaria
and angioedema with thyroxine. |
|
|
35: |
||
|
|
Theophylline as 'add-on' therapy
to cetirizine in patients with chronic idiopathic urticaria. A randomized,
double-blind, placebo-controlled pilot study. |
|
|
36: |
Nettis E,
Colanardi MC, Barra L, Ferrannini A, Vacca A, Tursi A. |
|
|
|
Levocetirizine in the treatment
of chronic idiopathic urticaria: a randomized, double-blind,
placebo-controlled study. |
|
|
37: |
Staubach P, Eckhardt-Henn A, Dechene M,
Vonend A, Metz M, Magerl M, Breuer P, Maurer M. |
|
|
|
Quality of life in patients with
chronic urticaria is differentially impaired and determined by psychiatric
comorbidity. |
|
|
38: |
||
|
|
Wheat induced urticaria? |
|
|
39: |
||
|
|
House dust mite sensitivity is a
factor in chronic urticaria. |
|
|
40: |
|||
|
|
In chronic idiopathic urticaria
autoantibodies against Fc epsilonRII/CD23 induce histamine release via
eosinophil activation. |
||
|
41: |
|||
|
|
Toxocara canis and chronic
urticaria in Egyptian patients. |
||
|
42: |
||
|
|
Cold urticaria: a case report
and review of the literature. |
|
|
43: |
||
|
|
Urticaria: selected highlights
and recent advances. |
|
|
44: |
||
|
|
Acquired angioedema secondary to
hormone replacement therapy. |
|
|
45: |
||
|
|
Contact urticaria to giraffe
hair. |
|
|
46: |
||
|
|
Urticaria associated with
parenteral nutrition. |
|
|
47: |
||
|
|
Review of H1 antihistamines in
the treatment of chronic idiopathic urticaria. |
|
|
48: |
||
|
|
Acute urticaria following
'gomutra' (cow's urine) gargles. |
|
|
49: |
Kalogeromitros D, Kempuraj D, Katsarou-Katsari
A, Gregoriou S, Makris M, Boucher W, Theoharides TC. |
|
|
|
Theophylline as
"add-on" therapy in patients with delayed pressure urticaria: a
prospective self-controlled study. |
|
|
50: |
||
|
|
Idiopathic chronic urticaria and
celiac disease. |
|
|
51: |
||
|
|
The thyroid and urticaria. |
|
|
52: |
||
|
|
Autoantibodies to the
high-affinity IgE receptor in chronic urticaria: how important are they? |
|
|
53: |
||
|
|
IgE-mediated allergy against
human seminal plasma. |
|
|
54: |
||
|
|
Assessing the therapeutic
benefits of antihistamines for the treatment of chronic idiopathic
urticaria--a requirement for well-designed comparative clinical studies. |
|
|
55: |
||
|
|
Cold urticaria; disease course
and outcome--an investigation of 85 patients before and after therapy. |
|
|
56: |
O'Donnell BF, Francis DM, Swana GT, Seed
PT, Kobza Black A, Greaves MW. |
|
|
|
Thyroid autoimmunity in chronic
urticaria. |
|
|
57: |
Fukunaga A, Bito T, Tsuru K, Oohashi A, Yu
X, Ichihashi M, Nishigori C, Horikawa T. |
|
|
|
Responsiveness to autologous
sweat and serum in cholinergic urticaria classifies its clinical subtypes. |
|
|
58: |
||
|
|
The effectiveness of montelukast
for the treatment of anti-histamine-resistant chronic urticaria. |
|
|
59: |
Kaplan AP, Spector SL, Meeves S, Liao Y, Varghese
ST, Georges G. |
|
|
|
Once-daily fexofenadine
treatment for chronic idiopathic urticaria: a multicenter, randomized,
double-blind, placebo-controlled study. |
|
|
60: |
|||
|
|
A new tool to evaluate the
impact of chronic urticaria on quality of life: chronic urticaria quality of
life questionnaire (CU-QoL). |
||
|
61: |
|||
|
|
Mechanism of chronic urticaria
exacerbation by aspirin. |
||
|
62: |
||
|
|
Chronic urticaria and thyroid
auto-immunity. |
|