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ALLERGIC SKIN DISEASE
(URTIKARIA, ANGIOEDEMA)
LABORATORY TEST
GROUP MEMBERS OF SGD B3:
CITRA GADING 0902005010
NI PUTU SUNTIAWATI 0902005053
KEVIN LEORNARD SURYADINATA 0902005087
YUDI ARTHA 0902005132
UVARANI VEERASAMY 0902005221
NUR ILYANA BINTI JAMALUDIN 0902005211
JAGTISH RAJENDRAN 0902005200
POTHANANTHA RAJA PATHMANATHAN 0902005189
SHANTINE THARUMANATHAN 0902005191
SEMESTER III
FACULTY OF MEDICINE
UDAYANA UNIVERSITY
2011
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CONTENT
NO. CONTENT PAGE
1 Chapter 1: Introduction
2. Chapter 2 : Content
2.1 Diagnostic Approach
2.2 Laboratory Studies
2.3 Diagnostic Tests
2.4 Specific findings
3. Chapter 3: Conclusion
4. References
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Introduction
Definition
Superficial itchy swellings of the skin due to transient plasma leakage from small blood vessels
are known as weals. Deeper swellings of the skin and alimentary tract are called angio-oedema.
These may be painful rather than itchy and tend to last longer. Weals and angiooedema
often coexist but either may occur alone. Most urticaria patients do not have systemic reactions
but, very rarely, physical urticarias may progress to anaphylaxis. Conversely, urticaria is often a
feature of anaphylactic and anaphylactoid reactions.[7]
There are two distinct types of urticaria called Ordinary Urticaria and Physical Urticaria.
Ordinary urticaria has two patternsAcute Urticaria and Chronic Urticaria.
Acute ordinary urticaria is often caused by an allergy to food, insect sting or
medication and can last between several hours and six weeks
Chronic ordinary urticaria is diagnosed if the rash persists for six weeks or longer, the
underlying cause is then usually not due to food allergies
All forms of urticaria may occur in association with deeper skin swelling or angioedema and
equally, angioedema may occur in isolation with no apparent urticaria. This depends on whether
we release histamine into the skin (urticaria), deeper tissues (angioedema) or both. Angioedema
swelling is most apparent in lax tissues around the eyelids, lips, tongue and genitals. This is also
referred to as Angioneurotic oedema and can be associated with Anaphylactic shock.[2]
What are hives (urticaria)?
Hives (medically known as urticaria) are red, itchy, raised areas of skin that appear in varying
shapes and sizes. They range in size from a few millimeters to several inches in diameter. Hives
can be round, or they can form rings or large patches. Wheals (welts), red lesions with a red
"flare" at the borders, are another manifestation of hives. Hives can occur anywhere on the body,
such as the trunk, arms, and legs. [3]
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One hallmark of hives is their tendency to change size rapidly and to move around, disappearing
in one place and reappearing in other places, often in a matter of hours. Individual hives usually
last two to 24 hours. An outbreak that looks impressive, even alarming, first thing in the morning
can be completely gone by noon, only to be back in full force later in the day. Very few, if any
other skin diseases occur and then resolve so rapidly. Therefore, even if you have no evidence of
hives to show the doctor when you get to the office for examination, he or she can often establish
the diagnosis based upon the history of your symptoms. Because hives fluctuate so much and so
fast, it is helpful to bring along a photograph of what the outbreak looked like at its worst. [3]
Swelling deeper in the skin that may accompany hives is calledangioedema. This may be seen
on the hands and feet as well as on mucous membranes (with swelling of the lips or eyes that can
be as dramatic as it is brief.)
[3]
The above table shows the Classification of urticaria subtypes (presenting with wheals and/or
angioedema)[8]
http://www.medicinenet.com/script/main/art.asp?articlekey=2253http://www.medicinenet.com/script/main/art.asp?articlekey=2253http://www.medicinenet.com/script/main/art.asp?articlekey=2253http://www.medicinenet.com/script/main/art.asp?articlekey=10681http://www.medicinenet.com/script/main/art.asp?articlekey=10681http://www.medicinenet.com/script/main/art.asp?articlekey=2253 -
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Content
Diagnostic Approach[4]
Detailed history is essential for diagnosis.
o Personal and family history
o Current or previous medications, herbals, or supplements
o Relationship to food exposures (ingestion, inhalation, contact)
o Relationship of potential physical triggers: e.g., cold, exercise, heat, sweating,
pressure, sun (or light) exposure
o Exposure to infectious processes: e.g., a respiratory virus, viral hepatitis,
infectious mononucleosis
o Occupational exposure to allergens or irritants
o Any recent insect sting or bite
o Contact exposure due to allergens, allergen exposure by inhalation
o Complete review of systems to include systemic diseases: e.g., autoimmune,
connective tissue and lymphoproliferative disorders
Physical examination, with special attention to:
o Thyroid enlargement (suggesting an autoimmune process and/or hormonal
dysregulation)
o Lymphadenopathy or hepatosplenomegaly (suggesting an underlying
lymphoreticular neoplasm)
o Joint, renal, central nervous system, skin, or serous surface abnormalities
(suggesting a connective tissue disorder)
o Dermographism suggests physical urticaria.
Cold, heat, and light tests are available for these respective physical
Further evaluation based on presenting findings
o IgE measurement for suspected IgE-mediated food, drug, or insect allergy
o Skin testing for detection of specific IgE antibody to inhalants (e.g., animal
danders, pollens, molds)
o Complement studies to exclude hereditary or acquired C1 esterase inhibitor
deficiency
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Laboratory Studies
Skin tests or radioallergosorbent assay test (specific IgE)[1]
o Selected allergy tests can be performed if food allergy or stinging insect
hypersensitivity is suspected. This may be helpful for some cases of acute
urticaria but is rarely helpful in the evaluation of chronic urticaria.Skin testing
can be performed to detect hypersensitivity to a limited number of antibiotics.
Testing for pollen or other inhalants is generally not helpful unless a severe
allergy may be causing the urticaria, such as a severe allergy to pollens, cats, or
latex (these may manifest as contact urticaria).
o Routine allergy testing with a large battery of screening tests is not recommended.
o
A few research centers perform an autologous serum skin test, but it is not a well-established procedure currently.
Screening laboratory studies[1]
o Which laboratory tests, if any, to order for routine screening is very controversial.
o Many specialists order only a few select screening studies for patients who have
chronic urticaria lasting at least 6 weeks with no apparent etiology.
o Some choose to perform no testing at all. Laboratory testing for acute urticaria is
not indicated, unless a particular medical condition is suspected.
o Common screening laboratory tests that may be ordered are as follows:
CBC with differential
Total eosinophil count
Sedimentation rate
Urinalysis
Liver function tests
o Evaluation of the complement system, including total hemolytic complement
(CH50), C3, and C4 should be considered in patients with prominent angioedema
(eg, C1 inhibitor deficiency causes angioedema but not urticaria) and may be of
benefit in patients with urticarial lesions lasting more than 24 hours. These tests
are of no value in patients with classic chronic urticaria.
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o Thyroid studies, including thyroid autoantibody levels (antimicrosomal,
antithyroglobulin) can be considered, particularly in women or in patients with a
family history of thyroid disease or other autoimmune diseases, although the
clinical significance of finding positive titers in a euthyroid individual is still
unclear.
o Order laboratory tests only if an abnormal result is found on the initial screening
tests or if a specific medical condition is suspected. Evaluation for possible occult
infection can be considered, but evidence that infections cause chronic urticaria is
limited.
o Other tests to consider if the history and physical examination findings are
suggestive of specific problems include the following:
Chemistry panel
Stool analysis for ova and parasites
H pylori workup
Hepatitis B and C workup
Sinus radiography (if symptomatic)
Antinuclear antibody (ANA)
Rheumatoid factor
Cryoglobulin levels
Other imaging studies
o Assays for serum histaminereleasing factors and evaluation for specific
autoantibodies (anti-IgE receptor/anti-FcR1 and anti-IgE) have been performed
by some research centers, and in-vitro assays geared toward measuring the
activity of anti-FcR1 autoantibodies can now be ordered through certain
commercial laboratories.Currently, 2 reference labs in the United States
commercially offer such a test: IBT Reference Laboratory (with the test referred
to as the CU IndexTM) and Clinical Reference Laboratories at National Jewish
Medical and Research Center (with the test referred to as the Anti-FcRI
antibody).The clinical role of a positive versus negative test finding on these
assays is still unclear, as current evidence does not make clear whether a positive
result should change management.
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Diagnostic tests[5]
Tests to consider:-
Tests to consider table for Urticaria and angio-oedema
Test Result
FBC with differential
Non-specific test that should be considered if performing alaboratory evaluation for chronic urticaria with or without
angio-oedema.
May provide evidence of occult infection, anaemia or findingssuggestive of chronic illness.
Also establishes a baseline for monitoring necessary with
some drug therapies.
may be normal orabnormal
complete metabolic panel
Non-specific test that should be considered if performing alaboratory evaluation for chronic urticaria with or withoutangio-oedema.
May provide evidence of chronic illness, such as hepatitis ornephritis.
Also establishes a baseline for monitoring necessary with
some drug therapies.
may be normal or
abnormal
urinalysis
Non-specific test that should be considered if performing a
laboratory evaluation for chronic urticaria with or withoutangio-oedema, especially in women.
May demonstrate asymptomatic bacteriuria, particularly infemale patients.
may show bacteriuria orpresence of white cells
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ESR
Non-specific test that should be considered if performing alaboratory evaluation for chronic urticaria with or withoutangio-oedema, especially if lesions are atypical.
Provides non-specific evidence of inflammation and/or apossible vasculitic component.
elevated
C-reactive protein
Non-specific test that should be considered if performing alaboratory evaluation for chronic urticaria with or without
angio-oedema, especially if lesions are atypical.
Provides non-specific evidence of inflammation and/or a
possible vasculitic component.
elevated
anti-IgE receptor antibody and related tests
Can only be ordered in specialised laboratories (can bereplaced with an autologous serum skin test depending on
availability).
Helps elucidate aetiology of chronic urticaria with or without
angio-oedema and often reassures both the patient and thephysician that there are no exogenous factors causing the
condition. The value of this test is controversial.
May provide evidence supporting an autoimmune aetiology of
chronic urticaria.
positive in autoimmune-related chronic urticaria
thyroid-stimulating hormone (TSH)
Should be accompanied by antithyroid antibodies test.
May reveal evidence supporting a diagnosis of
hypothyroidism and establishes a baseline value for potentialtherapy with thyroid replacement hormone.
elevated or normal
antithyroid antibodies
May help elucidate aetiology of chronic urticaria with orwithout angio-oedema. Should be accompanied by a TSH test.
Although the association of antithyroid antibodies and chronicurticaria is accepted, the value of this finding remains
controversial.
positive in Hashimotothyroiditis
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ANA
Only ordered if indicated by history and/or physicalexamination.
May provide evidence of underlying rheumatological disorder.
positive in many
rheumatological diseases
serum protein electrophoresis (SPEP)
Only ordered if indicated by history and/or physicalexamination.
May provide evidence of underlying haematologicalmalignancy.
may show increasedlevels of gamma
globulin
Helicobacter pylori antibody
Ordered when there is a history suggestive of oesophagealreflux or peptic ulcer disease.
positive in Helicobacter
pylori infection
skin prick testing for specific food allergens
Only ordered if history is suggestive of specific food allergies.Although controversial, it may also be ordered to reassure
patient and/or physician that food is not playing a role in
chronic urticaria. One must be aware of the possibility offalse-positive results, especially if a specific allergy is not
suggested by the history.
Positive results must be further evaluated with an elimination
diet and subsequent re-challenge of foods.
positive in urticaria
related to food allergy
in vitro IgE testing for specific food allergens
Can be used instead of percutaneous skin tests in patientsalready receiving antihistamines.
Only ordered if history is suggestive of specific food allergies.
Although controversial, it may also be ordered to reassurepatient and/or physician that food is not playing a role in
chronic urticaria. One must be aware of the possibility of
false-positive results, especially if a specific allergy is notsuggested by the history.
Positive results must be further evaluated with an eliminationdiet and subsequent re-challenge of foods.
positive in urticariarelated to food allergy
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skin biopsy
Sample is sent for standard staining and immunofluorescence
studies.
may show urticarial
vasculitis in setting ofatypical urticarial lesions
C4 level
Ordered in cases of angio-oedema without urticaria. A lowlevel is suggestive of either hereditary or acquired angio-
oedema.
decreased in hereditary
and acquired angio-oedema
C1-esterase inhibitor level
Ordered in cases with a high suspicion of hereditary angio-
oedema. A low level is highly suggestive of the diagnosis.
Rarely, patients can have normal levels of C1-esterase
inhibitor yet low function.
decreased in hereditary
angio-oedema
C1-esterase inhibitor function
Given that rare patients can have normal levels of C1-esterase
inhibitor yet low function, this test is ordered in cases with a
high suspicion of hereditary angio-oedema, with a low levelconfirming the diagnosis.
decreased in hereditary
angio-oedema
C1q levels
Ordered to help differentiate between hereditary and acquiredangio-oedema.
normal levels in
hereditary angio-oedema; low levels in
acquired angio-oedema
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The above table recommended diagnostic tests in frequent urticaria subtypes.[6]
Specific findings[4]
IgE-dependent
o No leukocytosis, elevated ESR, or hypocomplementemia
o With or without elevated total IgG
o With or without peripheral eosinophilia
o Allergen-specific IgE assay in serum (increased total IgE level or peripheral
eosinophilia)
Hereditary angioedema
o C1 inhibitor antigen (type 1) deficiency
o Normal C1 levels
o Decreased C4 and C2 levels (especially during attacks)
o Nonfunctional protein (type 2)
o Increased bradykinin level
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Acquired angioedema
o Decreased C1 function and C1q protein level
o Decreased C1 inhibitor, C4, and C2 levels
o Increased bradykinin level
Angiotensin-converting enzyme inhibitorelicited angioedema
o Increased bradykinin level
Conclusion
Hives (medically known as urticaria) are red, itchy, raised areas of skin that appear in
varying shapes and sizes.
Hives are very common and most often are not associated with a known cause.
Hives can change size rapidly and to move around, disappearing in one place and
reappearing in other places, often in a matter of hours.
Ordinary hives flare up suddenly and usually for no specific reason.
Physical hives are hives produced by direct physical stimulation of the skin.
Treatment of hives is directed at symptom relief while the condition goes away on its
own.
Antihistamines are the most common treatment for hives.
Hives typically are not associated with long-term or serious complications
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REFERENCES
1. Sheikh J,Najib U,Urticaria. 2010:emedicine.medscape.com2. Powell RJ, du Toit GL, Siddique N et al, BSACI guidelines for the management of
chronic urticaria and angio-oedema. Clin Exp Allergy 2007: 37; 631-650.
3.
Bolognia, Jean L., Joseph L. Jorizzo, and Ronald P. Rapini.Dermatology. 2nd ed. Spain:Mosby, 2008.
4. Zuraw BL: Clinical practice. Hereditary angioedema.N Engl J Med359:1027, 2008[PMID:18768946]
5. http://bestpractice.bmj.com/best-practice/monograph/844/diagnosis/tests.html6. Zuberbier et al. EAACI/GA2LEN/EDF guideline: definition, classification and diagnosis
of urticaria Allergy 2006: 61: 316320
7. C.GRATTAN, S.POWELL* AND F.HUMPHREYS, Management and diagnosticguidelines for urticaria and angio-oedema, British Journal of Dermatology 2001; 144:708714
8. Zuberbier et al. EAACI/GA2LEN/EDF guideline: definition, classification and diagnosisof urticaria Allergy 2009: 64: 14171426
http://www.unboundmedicine.com/medline/ebm/record/18768946/full_citationhttp://bestpractice.bmj.com/best-practice/monograph/844/diagnosis/tests.htmlhttp://bestpractice.bmj.com/best-practice/monograph/844/diagnosis/tests.htmlhttp://www.unboundmedicine.com/medline/ebm/record/18768946/full_citation