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CHRONIC AND ACUTE
URTICARIA IN CHILDREN
Dr. Kessel Aharon , Department of
Allergy and Clinical Immunology
Bnai-Zion,2007
Urticaria, is characterized by transient,
itchy, elevated edematous wheals or red
papules.
Wheal typical
features
# A central swelling,
surrounded by erythema.
# Itching or burning
sensations
# The wheal disappear
usually within 1-24 h.
Angioedema
# Pronounced swelling of the
lower dermis and subcutis.
# Most often found in the lips,
eyelids or genitalia.
# Itching and sometimes pain.
# Resolution can take up to
72h.
# It is associated with urticaria
in about 40% of cases.
The histology of the lesions of chronic idiopathic urticaria
Venule and capillary dilatation
tissue edema –upper and mid dermis.
predominantly perivascular cellular infiltrate – primarily mononuclear cells
T cell are the predominant cell type
(80%)
Mild to moderate increase of mast
Cell numbers
Clinical classification of urticaria
and angioedema
• Ordinary urticaria- acute , chronic, episodic.
• Physical urticaria
• Angioedema
• Contact urticaria
• Urticarial vasculitis
Clinical classification of urticaria
and angioedema
Ordinary urticaria
Acute- up to 6 weeks of continuous activity
Chronic – 6 weeks or more of continuous
Episodic (intermittent)
‫מה היא הסיבה השכיחה ביותר שניתן‬
‫למצוא כגורמת לאורטיקריה חריפה ?‬
‫‪ .1‬אלרגיה לתרופות‬
‫‪ .2‬מחלות זיהומיות‬
‫‪ .3‬עקיצות חרקים‬
‫‪ .4‬חומרי ניגוד‬
‫‪ .5‬אלרגיה למזון‬
57 children age range 1-36 months
Presumptive cause
Viral infection 18 cases (12 associated with
drug intake)
Adenovirus
ROTA virus
EBV
Enterovirus
RSV
Varicella-Zoster virus
BACTERIAL INFECTION 1 CASE– E.COLI
FOOD -6 cases
Probable cause (27 cases)– viral infections
Mortureux P, et al Archives of dermatology 1998;143:319-23.
Acute urticaria
• Infections-
viral :herpes simplex, hepatitis B,
coxsackie A and B, upper respiratory infections.
• Bacterial- associated with certain infectious foci:
dental caries/abscesses, pharyngitis /tonsillitis,
otitis media, occult abscesses, UTI.
• Parasitic : ascaris, strongyloides, echinococcus,
toxocara, fasciola, filaria, schistosoma.
• Fungal?: candida
Acute urticaria
• Exposure to food allergens- milk, eggs,
peanuts,
sesame ,soy wheat, shellfish, fish.
• Medications-β-lactam antibiotics,
sulfonamides, aspirin.
• Radiocontrast media
‫ילדה בת ‪ 4‬שנים מגיעה לחדר מיון עם אוטיקריה‪ ,‬היא‬
‫מטופלת ע"י רופא מטפל באנטיהיסטמינקה למרות כך‬
‫עדיין הפריחה קיימת‪.‬‬
‫האם מתן קורטיקוסטרואידים‬
‫בנוסף לאנטיהיסטמיניקה‬
‫עוזר בטיפול באורטיקריה‬
‫חריפה ?‬
Treatment of acute urticaria
Ann Emerg Med. 1995 Nov;26(5):547-51.
Short Outpatient management of acute urticaria: the role of prednisone.
CONCLUSION: The addition of a prednisone
burst improves the symptomatic and clinical
response of acute urticaria to
antihistamines. Patients' conditions
improved more quickly and more completely
when prednisone was administered, without
any apparent adverse effects.
ALGORITHM FOR ACUTE
URTICARIA/ANGIOEDEMA
DETAILED HISTORY: infection
drug
food
physical triggers
PHYSICAL EXAMINATION
SPECIFIC EXAMINATION- CBC , URINE, ESR
SKIN TESTS
IgE-dependent (type -1)
Skin Prick Test (SPT)
Positive reaction
SYNDROMYES THAT CAN BE
ASSOCIATED WITH URTICARIA
Muckle-Wells syndrome
Familial -dominantly inherited.
urticaria
progressive nerve deafness
Limb pain
arthritis
Recurrent fever
hypergammaglobulinemia
amyloidosis
Gleich's syndrome - the episodic
angioedema with eosinophilia
syndrome
Schnitzler syndrome (SS), first reported in
1972, is characterized by chronic,
nonpruritic urticaria in association with
recurrent fever, bone pain, arthralgia or
arthritis, and a monoclonal immunoglobulin
M (IgM) gammopathy in a concentration that
is usually less than 10 g/dL.
Chronic Urticaria – 6 weeks or more of
continuous urticaria.
‫מה היא הסיבה השכיחה ביותר לאורטיקריה‬
‫כרונית ?‬
‫‪ .1‬אלרגיה לתרופות‬
‫‪ .2‬גורמים זיהומיים‬
‫‪ .3‬אידיופטי‬
‫‪ .4‬מנגנון אוטואימוני‬
‫‪ .5‬אלרגיה למזון‬
‫‪ .6‬דלקת מפרקים של גיל הילדות‬
‫‪ 93‬ילדים (‪-52‬זכרים ‪ 41 ,‬נקבות ‪ ,‬גיל ממצוע ‪ 7.8‬שנים )‬
‫אורטיקריה‪-‬אידיופטית ‪31%‬‬
‫אורטיקריה אוטואימונית ‪29%‬‬
‫אורטיקריה עקב גורם זיהומי ‪15%‬‬
‫אורטיקריה פיזיקאלית ‪12%‬‬
‫אורטיקריה מולטיפקטוריאלית ‪11%‬‬
‫אורטיקריה אלרגית – ‪2%‬‬
‫‪Brunetti et al.‬‬
‫‪J Allergy Clin Immunol 2004;114:922-7‬‬
Autoimmune urticaria
In 1986 Grattan first
described that:
Autologous serum test
produces a
Wheal and Flare
reaction
In 30-50% of CIU
cases
Autoimmune (autoantibodies against FcεRI or IgE)
In 1993 M. Greaves first
found the presence of autoantibodies in CIU.
N Engl J Med 1993;328:1599-604
In vitro studies demonstrated that
75% of autoAb are IgG against FceR
(causing in-vitro human basophil
degranulation)
15% were IgG against IgE
(cross-linking two IgEs on mast cells)
Autoimmune basis for CIU
Thyroid autoimmunity in pts with CIU
anti-thyroid Ab. in 14-20%
increased / decreased thyroid
function in 5-10%
Immune aberrations- basis for CIU
Activated T cell
express increased
expression of CD40L
B and T cell
lymphocytes derived
from active CU
patients
demonstrated an
increase expression
of bcl-2.
Toubi et al. J Clin Immuno 2000;20:371-378
Physical urticaria
The physical urticarias are characterized
by the development of wealing and
itching promptly after application of the
appropriate physical stimulus.
Weals typically fade within 30-60 minutes. The
exception is delayed pressure urticaria when the
weals take several hours to appear after
sustained pressure and can last up to 48 hours.
Physical urticaria-cholinergic
Itchy,
monomorphic
pale or pink
wheals on trunk,
neck, and limbs –
after exercise or
a hot shower
Prevalence of 11% in the age group of 16-35
years.
Physical urticaria-pressure
Large painful or itchy red
swelling at sites of
pressure (soles, palms, or
waist) lasting 24 hours or
more- application of
pressure perpendicular to
skin produces red
swelling after a latent
period of 1 to 4 hours.
Physical urticaria- dermographic urticaria
Itchy, linear wheals with
surrounding bright-red flare at
sites of scratching or rubbing.
Physical urticaria- dermographic urticaria
# The most
frequent form of
physical urticaria.
# Affecting mainly
young adults
# Mean duration
6.5 years
Physical urticaria- heat
A rare form of
urticaria.
nduced by direct
contact of the skin
with warm objects or
warm air.
The eliciting
temperature ranges
from 38º C to more
than 50 º C .
Physical urticaria- cold
Itchy pale or red
swelling at sites of
contact with cold
surfaces or fluidsten minutes
application of an ice
pack causes a wheal
within five minutes of
the removal of ice.
Physical urticaria- cold
More frequent in women than
men.
Majority is idiopathic, some
can also occur as a result of
infections, neoplasia or
autoimmune diseases.
Infectious: syphilis, measles
hepatitis ,mononucleosis,
HIV.
Other forms of physical urticaria
Solar
Vibratory
Adrenergic
aquagenic
Role of nonallergic hypersensitivity
reactions in children with chronic
urticaria ~ 5 %
Food –symptoms clears within 48 hours if relevant
food allergens are eliminated.
Food additives
Elimination pseudoallergen diet - for at least 2-3
weeks before beneficial effect seen.
Allergy 1998:53:1074-7
The prevalence in different studies ~ 5-10%
Viruses- hepatitis B,C , EBV , CMV
Bacteria- helicobacter pylori ?
streptococci/staphylococci
parasites -Anecdotal series of cases
documented a link between parasites and
chronic urticaria such as: toxocara canis,
giaardia lamblia, strongyloides stercoralis
and even blastocytis hominis.
Urticarial vasculitis
Urticarial vasculitis
IDIOPATHIC URTICARIA
•Do not have a predominantly physical trigger.
•Are not caused by underlying vasculitis.
•Are not caused by direct contact with the
causative agent.
•This heterogeneous group includes: cases for
which no cause can be identified.
CU Duration ??
* Patients ask, how long CU will last ??
* More than 60% still visit the clinic
after 6 months.
* 40% of patients still suffer from CU
after one year.
Clinical and Laboratory Parameters in Predicting Chronic Urticaria
Duration: A Prospective Study of 139 Patients
100
90
94%
80
70
75%
60
50
52%
43%
40
30
20
14%
10
60
36
24
12
Urticaria duration (months)
Toubi et al Allergy:2003
6
0
CU%
Rates of urticaria duration in relation to disease severity
severity
Rates of urticaria cure
12m*
68%
mild
(n = 23)
moderate – severe 86%
(n = 116)
24m
0%
59%
36m
50%
p value
60m
32%
<
0.0001
TREATMENT OF CHRONIC
URTICARIA
• Daily non-sedating antihistamine
• Combination of H1 and H2 receptors
antagonists
• Corticosteroids
TREATMENT OF SEVERE
UNREMITTING URTICARIA
• Plasmapheresis
• Intravenous immunoglobulin
• Cyclosporin A
Cyclosporine A
• cyclosporine on helper T-cells to inhibit Tcell receptor- activated induction of IL-2
gene.
• cyclosporine may also inhibit IgEstimulated mast cell degranulation and
stimulate TGF- expression.
Low dose cyclosporin A in the treatment of severe
chronic idiopathic urticaria.
• 2-3mg\kg of CsA, was shown to be
beneficial
• AST Positivity could not predicted
response to treatment.
• In some cases Prolonged treatment is
needed
Toubi et al Allergy 1997;52:312-316.
ANGIOEDEMA
With weals
All kinds of
urticaria except
dermographism
Without weals
Idiopathic
DRUGS- NSAIDs ,ACEIs
C1 eterase deficiency
Complement-dependent (C1 esterase inh.Def.)
Complement-dependent (C1 esterase inh.Def.)
1 ‫אנגיואדמה תורשתית סוג‬
C4 –decreased , C1 esterasedecreased
2 ‫אנגיואדמה תורשתית סוג‬
C4 –decreased , C1 esterase-normal
‫אנגיואדמה אידיופטית‬
C4 –normal , C1 esterase-normal
CONTACT URTICARIA
Contact urticaria is an
important manifestation of
natural rubber latex allergy.
‫תאור מקרה‬
‫ל‪.‬ע בת ‪ 16‬שנים‬
‫הופנתה עקב אורטיקריה מזה כחצי שנה‪.‬‬
‫סקירה מערכתית ‪ :‬עליה במשקל של כ‪ 5‬ק"ג בחצי‬
‫שנה ‪,‬עייפות‪.‬‬
‫בדיקה גופנית אורטיקריה קלה בעיקר בבטן וגב –‬
‫בולטת יותר באזורי לחץ ‪.‬‬
‫בדיקות מעבדה ‪ :‬ס"ד ‪ ,‬תפקודי כבד ‪,‬כליה‪ ,‬שתן‬
‫כללית ‪,‬צואה לפרזיטים‪-‬ללא ממצא‪.‬‬
‫טסט עורי למוצרי מזון‪ -‬שלילי‬
‫‪ ,↑ 50 -TSH‬נוגדנים לרקמת בלוטת התריס‪.‬‬
‫‪ - AUTOLOGUS SERUM TEST‬חיובי‪.‬‬
‫טיפול – מתן אלטרוקסין‬
‫לורסטין ‪ 10‬מ"ג‬