CONCENSUS STATEMENT

FOR THE DIAGNOSIS AND

TREATMENT OF URTICARIA:
A 2017 UPDATE
Journal Reading
Tiara Nadya P
Pembimbing: dr. Hiendarto, Sp.KK
1810221029

Departemen Kulit
RSUD Ambarawa
Fakultas Kedokteran UPN “Veteran” Jakarta
 ABSTRACT
Underlying
Treatment
causes
2nd-generation
nonsedating
Elimination
H1-
antihistamines

Dose can be
Identification increased up to
4x

• severity of the symptoms

Appropriate • affordability of the drugs
treatment • accessibility of modern
options biologics such as omalizumab.
 DEFINITION
 Urticaria or hives is a common skin condition that
affects population with a lifetime prevalence of up to
22% and point prevalence of 1%.
 Urticaria
Central swelling of variable size
Surrounding reflex erythema
Associated symptoms of pruritus or burning

resolves within a few hours and always by 24 h

 Angioedema is typically characterized by sudden,
pronounced swelling of the lower dermis and subcutis

72 h for resolution
 CLASSIFICATIONS

Urticaria
Acute
Chronic Spontaneous
Urticaria (CSU)
Chronic
Chronic Inducible
Urticaria (CINDU)
 EPIDEMIOLOGY

CSU is known to be the most common form of CU (66 to

93% of cases)

CSU is a chronic disease whose duration is estimated

to be 1–5 years on an average.
50% resolves within 6 months of onset
20% resolves within 3 years
20% resolves within 5–10 years
2% of CSU cases may take up to 25 years to resolve.
CSU can persist for up to 50 years.
PATHOPHYSIOLOGY
ASSESSMENT TOOLS
 DIAGNOSIS

Routine
laboratory
Patient history Physical examination investigations 
autoimmune or
autoinflammatory
disease

• Time of onset of disease

• Presence of any precipitating factors; association with angioedema
• Persistence of individual wheal beyond 24 h
• Use of drugs (NSAIDs, ACE inhibitors, immunisations, hormones, and alternative
remedies)
• Quality of life (QOL)
• Treatment history
 MANAGEMENT

Elimination or avoidance of the cause or trigger/stimulus

Symptomatic pharmacological treatment by reducing mast cell mediator release and/or the effect of
these mediators at the target organ, and inducing tolerance.

Identifying the cause of urticaria is not possible in most cases; however, good history to rule out
causes of inducible urticaria will increase therapeutic efficiency

Elimination of the drug wherever possible is suggested (NSAID, ACE Inhibitors).

CSU is often anecdotally reported to be associated with a variety of inflammatory or infectious diseases.
These infections include those of the GI tract, such as H. Pylori, should be eliminated if the treating
physician feels in select cases.
 TREATMENT
 First-line therapy
Second-generation nonsedating antihistamines
• The first-generation antihistamines are reported to have potent anticholinergic
effects and sedative actions on CNS lasting longer than 12 h, with therapeutic
actions only for 4–6 h. Most of them cross blood–brain barrier and interact with
brain H1-receptor, leading to disturbed rapid eye movement sleep and cognitive
functions.
• Many drug-drug interactions were also reported for sedating antihistamines.
• modern lowcost second-generation antihistamines with lesser side effects, without
anticholinergic effect (no sedation and cognitive dysfunction) and also with higher
efficacy and duration of action, thus better compliance.
 Only seven of them (cetirizine, desloratadine,
fexofenadine, levocetirizine, loratadine,
rupatadine, and bilastine ) have been tested in details
in urticaria.
 Three of the commonly used second -generation
antihistamines in India ( desloratadine, fexofenadine,
and levocetirizine) were extensively evaluated in the
management of urticaria for safety and efficacy even up
to four-fold elevation of the standard doses .
 Inhibition of cell adhesion molecules-1, endothelial
leukocyte adhesion molecule-1 expression, generation
and release of cytokines, and inhibition of eosinophil
chemotaxis.
 Second line therapy
Up-dosing of second-generation nonsedating
antihistamines
 Studies confirmed the absence of dose -related QT
interval prolongation with high doses of fexofenadine as
up to 800 mg once daily or 690 mg twice daily for
28 days establishing the safety of the drug in higher
doses
 Other drugs with good safety and efficacy data on 4-
time elevation standard doses are cetirizine,
levocetirizine, and desloratadine
 Since levocetirizine is the active enantiomer of
cetirizine, the present guideline recommends that only
levocetirizine, fexofenadine, and desloratadine
should be considered for 4-time elevation, till better
safety and efficacy data are available for other
molecules.
 Corticosteroids Cyclosporine

• 2 months of • cyclosporine at doses of

methylprednisolone 16 3–5 mg/kg/day for 16
mg along with weeks along with daily
levocetirizine 5 mg daily cetirizine was reported
 significant reduction to significantly
in mean UAS. ameliorate symptoms of
• systemic steroids are CSU patients
recommended to be • continuous blood
used sparingly only for a pressure and blood urea
short period and creatinine
monitoring are required
during the course of
therapy.
OMALIZUMAB
 Humanised monoclonal IgG Antibody against IgE
 A double-blind RCT over 323 refractory urticaria
patients with moderate-to severe CSU demonstrated
a high outcome with omalizumab 150 mg or 300
mg subcutaneous [SC] injection at every 4 weeks
apart for 12 weeks.
 Several more case series and reports conform
omalizumab superiority in the treatment of
refractory cases of CSU/CINDU
 1st gen antihistamin H2-blockers

•in select cases, •combinations of H1-

hydroxyzine may be and H2-antihistamines
used in refractory in a smaller number of
cases because of easy CU patients reported
availability, cheaper better outcome than
costs, and long H1-antihistamines
experience of the alone but also pointed
Indian doctors using out the weak level of
the molecule. evidence
•Against random or
routine use of H2-
blockers
 Methotrexate Autologous Serum Therapy

• methotrexate (15 mg • The present consensus

weekly) for 3 months in suggests that AST may be
refractory CU cases did tried in refractory urticaria
not show any significant for its low cost and good
additional benefit over safety profile, but
H1-antihistamines. evidence for potential
• may be considered as an benefit is low.
alternative in selected
cases of refractory
urticaria especially in
Indian perspective, for its
low cost, easy availability,
easy dosing schedule and
wide acceptance
 Montelukast Dapsone

•Leukotriene antagonist •Dapsone is known to confer with

montelukast at 10 mg/day was side effects such as
reportedly effective for the methaemoglobinaemia,
treatment of CU, both as peripheral neuropathy,
monotherapy or in combination hepatotoxicity. Ruling out G6PD
with H1-antihistamines although deficiency is mandatory before
the treatment effect observed initiation of dapsone.
was small •Due to the lack of evidence and
•The present guidelines suggest possibility of serious side effects,
that there is no added advantage the consensus guidelines
of montelukast over standard recommend against the use of
antihistamines and therefore dapsone in the treatment of
should not be considered as CSU/CINDU.
therapeutic option in regular
basis and should only be
reserved as an adjuvant in select
refractory cases
 Miscellaneous
Doxepin hydroxychloroquine Mycophenolate
treatments
• can be used as a • The consensus • because of low • Tumour necrosis
third line of guideline evidence, doubtful factor-alpha
treatment in select recommends effect, high cost, antagonists in
cases of against the use of and incidence of cases of delayed
CSU/CINDU, hydroxychloroquine adverse effects pressure urticaria
especially when in urticaria. present guideline and IV
cyclosporine and suggests against immunoglobulin in
omalizumab are using of MMF in cases of refractory
unavailable, CSU/CINDU. CSU were used
inaccessible, or successfully in odd
contraindicated. case reports.
• UV-A1, PUVA, and
narrowband UV-B
were used as
adjuvant with
antihistamines for
refractory urticaria.
REKOMENDASI
In childrens Pregnancy & lactation Hepatic Impairment Renal Impairment

The dose of cetirizine,

Cetirizine, desloratadine, Mizolastine is levocetirizine, and
fexofenadine, levocetirizine, Best to avoid all contraindicated by hydroxyzine should be halved
and loratadine antihistamines in pregnancy significant hepatic in patients with impaired
impairment. renal failure.
Elimination of underlying
causes and/or eliciting There is no reports of Chlorphenamine and Cetirizine and levocetirizine
triggers wherever possible teratogenicity and birth hydroxyzine should also be should not be used in severe
defects in pregnant women avoided in severe liver renal impairment.
using modern second- disease because their
generation antihistamines sedating effect is
inappropriate. Loratadine and
desloratadine should be
Clinicians, because of its Other second-generation used with caution in severe
long safety record often antihistamine may be used renal impairment.
choose chlorpheniramine with caution weighing the
risk benefit ratio.
Cyclosporine is not
teratogenic, but it is
embryotoxic in animal
models and is associated
with preterm delivery and
low birth weight in human
infants
TERIMAKASIH