Urticaria part I

Urticaria
(Part I)
Onnicha Chaisetsumpan, MD
Division of Allergy, Immunology and
Rheumatology Unit, Department of Pediatrics
King Chulalongkorn Memorial Hospital

Definition
Wheal 3 typical features
• Central swelling of variable size, surrounded by reflex erythema
• Itching or burning sensation
• Skin returns to normal appearance within 30 minutes to 24 hours
Angioedema
• Sudden, pronounced erythematous or skin colored swelling
of lower dermis or subcutaneous mucous membrane
• Sometimes pain > itch
• Resolution slower than wheals, take up to 72 hours
Middleton’s Allergy Principle and Practice 9th edition, 2019
Clinical Immunology 5th edition

Epidemiology and prevalence
• 15-25% of population will experience an episode of urticaria in lifetime
• Mainly affects young adults, female predominant
• Chronic urticaria affects up to 1% of general population in US
• More common in adults, middle-age with women:men 2:1
• Uncommon in children and adolescents
• One-third of patients presents with hives and angioedema
• 30-40% isolated hives, 10-20% isolated angioedema
• Coexpression of allergic disease diagnosis in patients with chronic urticaria appears
to be slightly higher than general population
Middleton’s Allergy Principle and Practice 9th edition, 2019.

Pathogenesis
• Skin mast cells = key players in
pathogenesis of urticaria
• Predominantly located around small
blood vessels, lymphatic vessels and
peripheral nerves
• Membrane receptors: high-affinity IgE,
complement receptors, activation sites
for neuropeptides and basic
secretagogues

Activate sensory nerve
Itch
Preformed mediators from activated
mast cells: histamine, protease
(tryptase, chymase), heparin
Recruitment of cells in lesions
Elias J, et al. JACI 1986;78:914-8
Ying S,et al, JACI 2020;103:484-93
Ito Y et al, Allergy 2011;66-1106-13
Pathogenesis

Pathogenesis
Zuberbier T, et al, Allergy 201;69:868-87

Autoimmune theory
• Thyroidperoxidase
• IL-24
Type I autoallergy (autoreactive IgE)
Maurer M, et al. JACI in practice 2021 Mar 1;9(3):1067-78.
Altrichter S, et al. Allergy, Asthma & Immunology Research. 2021 Mar;13(2):206.

IL-24
1062 patients with chronic
spontaneous urticaria
7 patients with
idiopathic anaphylaxis
482 patients with
healthy control subjects
Schmetzer O, et al. JACI 2018 Sep 1;142(3):876-82.

Autoimmune theory
Type II Autoimmunity (Autoreactive IgG)
Altrichter S, et al. Allergy, Asthma & Immunology Research. 2021 Mar;13(2):206.

Role of eosinophils
Altrichter S, et al. JACI 2020 Jun 1;145(6):1510-6.

Mast cell dependent Mast cell independent
Immunological Non-immunological Pseudo-allergy Kinin-Mediated
angioedema
• Allergic urticaria
• Autoimmune urticaria
• Immune complex-
mediated urticarial rash
Neuropeptides
(substance P,
neuropeptide Y,
vasoactive intestinal
peptide,
somatostatin)
• Aspirin and other
NSAIDs
• Food-induced
pseudo-allergic
reactions in CSU
Etiological classification

Allergic urticaria
• Immunological mast-cell activation via high-
affinity IgE receptor; IgE-mediated urticaria
• Cross-linking of receptor-bound IgE à release
preformed and newly synthesized mediators
• Acute and chronic urticaria
• Resolve rapidly on withdrawal of allergen
exposure and recur with re-exposure to
allergen or cross-reactive agents
Mast cell dependent
Immunological Non-immunological
• Immune complex-
mediated urticarial
rash
Neuropeptides
(substance P,
neuropeptide Y,
peptide,
somatostatin)

Autoimmune urticaria
• Functional autoantibodies directed against
extracellular FcεRI or receptor-bound IgE
• Cross-linking of high-affinity IgE receptors by
autoantibodies
• IgG1, IgG3: fix complement
• Low-affinity IgE receptor FcεRII/CD23 on B
lymphocytes and eosinophils
• Anti-CD23 antibody detected in patients
with CSU
Mast cell dependent
• Immune complex-
mediated urticarial
rash
Neuropeptides
(substance P,
neuropeptide Y,
peptide,
somatostatin)

Immune complex-mediated urticarial rash
• Circulating immune complex binds to FcyRIII
• Activate complement —> C3a and C5a anaphylatoxin
formation
• Immune complex-mediated urticarial rash developed
1-3 weeks after initial exposure to antigen and
disappeared several weeks after antigen
discontinuation
Mast cell dependent
• Immune complex-
mediated urticarial
rash
Neuropeptides
(substance P,
neuropeptide Y,
peptide,
somatostatin)

Mast cell independent
Pseudo-allergy Kinin-Mediated
angioedema
• Aspirin and other
NSAIDs
• Food-induced
pseudo-allergic
reactions in CSU

• Urticarial lesion shows skin mast cells
degranulated in the dermis
• Perivascular leukocyte infiltrate composed of
lymphocytes, eosinophils, neutrophils and
basophils migrated to skin lesion
Skin histopathologic features

Classification
Thai CPG, Clinical immunology 5th
• Spontaneous urticaria
• Acute urticaria (AU)
• Chronic urticaria (CU)
• Inducible urticaria
• Occur when triggered by specific
physical stimuli
• Physical urticaria, aquagenic urticaria,
cholinergic urticaria, contact urticaria
Middleton 9th edition
•Acute urticaria
•Chronic urticaria
• Chronic inducible urticaria
• Chronic spontaneous urticaria
(chronic idiopathic urticaria)
Nelson Textbook of Pediatrics 21st edition

Classification
Spontaneous urticaria
• Most common presentation
• No assumption about etiology
• Acute, chronic, episodic urticaria
Limpongsanurak W, et al. Asian Pac J Allergy Immunol. 2016;34:190-200.

Classification
Zuberbier T, et al. Allergy 2014;69:868-87.

Acute urticaria
• Lasting less than 6 weeks
• Self-limited, spontaneous resolved within 3
weeks
• 10% of patients progress to chronic
spontaneous urticaria
• Often cause by allergic IgE-mediated reaction
• Precipitating factors identified in <50% of cases
• Infections are the most common (40%)
identifiable cause of acute urticaria
• Food = most common in young children

Chronic urticaria
•Chronic spontaneous urticaria 80%
•Chronic inducible urticaria 20%
• Presence of urticaria on most days of the weeks (at least 2 times per week)
and for more than 6 weeks
• Not recurrent acute urticaria with repeated exposure to specific antigen
• 40% of patients with chronic urticaria accompanying episodes of angioedema,
10% angioedema as main manifestation

Chronic inducible urticaria (CIndU)
Physical urticaria
External mechanical or thermal stimulation
• Pressured related physical urticaria
• Symptomatic dermographism
• Delayed pressure urticaria
• Vibratory angioedema
• Thermal or ultraviolet-induced urticaria
• Cold urticaria
• Heat urticaria
• Solar urticaria
Non-physical urticaria
Eliciting stimuli for mast cell degranulation
defined by nonphysical exposure
• Cholinergic urticaria
• Aquagenic urticaria
• Contact urticaria

EAACI/GA2LEN/EDF/UNEV recommendation 2016

Chronic inducible urticaria (CIndU)
• Recurrent wheals or angioedema as
response to specific triggers
• Common, estimated prevalence 0.5%
• Many patientis are severely disabled,
mainly due to impact of trigger
avoidance
• Female predominance (74%)
• Diagnosed by patient history and
results of provocation tests
Difference compared with
chronic spontaneous urticaria
• Longer duration
• Lower rate of remission at 1 yea
• Relatively brief duration of individual
wheals, lasting minutes to hours (expection
DPU)
• Systemic symptoms of mast cell activation
esp. cold urticaria, cholinergic urticaria

Therapeutic goal of chronic inducible urticaria
•Achieve complete symptom control
•Trigger avoidance
•Desensitization
•Blocking effects of mast cell mediators
•Prevention of mast cell degranulation
Maurer M, et al. JACI in practice 2018 Jul 1;6(4):1119-30.

Physical urticaria: Dermographism
• Most common physical urticaria 5% of general population
• Symptomatic dermographism (SD), urticaria factitial,
dermographic urticaria
• Mainly affect young person
• Clinical manifestation
• Typical red, itchy, linear wheal evoked within minutes of
stroking friction, rubbing or scratching skin
• Manifest rapidly after pressure application to skin
• Very rare cases, develop angioedema
• DDx simple urticaria, white dermographism (AD)
• Wheals without itch sensation, occur after stroking Middleton’s Allergy Principle and Practice 9th edition, 2019.

Physical urticaria: Dermographism
• Diagnosis:
• History
• Report pruritus without visible rash followed by linear wheals lasted minutes
• Chronic itch or skin crawling sensation leading to scratching
• Review photographs for linear wheals assisted diagnosis
• Stroking, scratching or pressure skin usually on upper back
• Skin test site should be free of infection or inflammation
• Positive: pruritic palpable wheal presented within 10 minutes of provocation
• With blunt firm object or calibrated instrument: dermographometer, Frictest
• Treatment: trigger avoidance, nonsedating second-generation H1 antihistamine

Physical urticaria: Delayed pressure urticaria
• Pressure-related physical urticaria
• Isolated DPU occurs 2% of all patients with urticaria
• Coexist with chronic spontaneous urticaria up to 40% of patients
• Sustained local pressure: wearing tight shoes, carrying heavy bags, long walks, sitting
or leaning against firm objects, jogging, driving or clapping hand
• Deep painful rather than itchy swelling resembling angioedema
• Delayed-onset: 30 minutes to 12 hours after pressure (typical 4-6 hours)
• May associated with flu-like symptoms, fever, arthralgia, fatigue
• Most frequent sites: hands, soles, buttocks, shoulders, areas under straps
• Lesion last 12-48 hours Nelson Textbook of Pediatrics 21st edition

Physical urticaria: Delayed pressure urticaria
• Diagnosis
• Transient leukocytosis, elevated ESR
• Challenge test: Hanging heavy weight suspended on narrow band over
the forearm or thigh for 15 minutes
• More reliable results:
• Obtained dermographometer applied at 100 g/mm3 for 70 seconds
• Assess reaction after 2-6 hours, record symptoms over 24 hours
• Skin biopsy: evidences of neutrophils and eosinophils
• Treatment
• Avoid tight fitting, clothing
• Difficult to treat, poorly respond to antihistamine
• Antihistamine with LTRA, prednisolone, anti-TNF
Positive: red palpable swelling at
test site 6 hours after application

Physical urticaria: Vibratory angioedema
• Rare condition
• Familial cases have been described
• Local swelling
• Develops several minutes to 6 hours
• After using vibrating machinery, lawn
mowing, applauding ang jogging
• Systemic symptoms may occur
headache, chest tightness, diffuse flare
• Diagnosis
• Placing elbow or hand on laboratory
vortex for 5-15 minutes
• Treatment
• Avoidance of trigger is the only helpful
treatment strategy
• Antihistamine

Physical urticaria: Cold urticaria
• 3% of physical urticaria, second most
common subtype of physical urticaria
• Occurs in both children and adults
• More common in cold climates, women
and atopic patients
• Majority of cases are primary, no
identifiable cause
• Primary and secondary: typical positive
response to cold provocation
1-5% secondary causes
• Cryoproteins, mainly cryoglobulins
• Infection: hepatitis C, infectious
mononucleosis, syphilis, Mycoplasma
infection
• Autoimmune disease
• Lymphoreticular malignancy: Waldenstrom
macroglobulinemia, myeloma
• Drug: penicillin, oral contraceptives, ACEIs

Maltseva N, et al. Allergy. 2021 Apr;76(4):1077-94.

• Evoked by low ambient temperature,
contact with cold objects, food or
beverages, immersion in cold water
• Mucosal involvement may develop after
drinking cold beverage
• Symptoms occur within minutes after skin
contact and persist approximately 1 hour
• Wheals more common developed during
rewarming
• Local or generalized
• Systemic symptoms
• Respiratory: laryngeal angioedema, tongue
or pharyngeal swelling, wheezing
• GI: hyperacidity, nausea, diarrhea
• Neuro: disorientation, headache
• Severity of cold urticaria depends on intensity
and duration of cold stimulus
• Risk of anaphylaxis and death on exposure
to large skin areas

Diagnosis: Applying defined cold stimulus to surface
of volar forearm for 5 minutes
• Threshold testing: time and temperature
• Ice cube test
• Cool packs, cold water baths should not be
performed due to risk of systemic reactions
• Ice cube placed within thin plastic bag (avoid cold
damage, prevent direct water contact: false
positive in aquagenic urticaria)
• Develop urticaria at rewarming time
• TempTest

Some atypical cold-induced urticaria: negative results

• Treatment
• Avoid prolonged skin contact with cold objects or exposure to air temperature
below threshold temperature
• Antihistamine: helpful but not provided complete protection
• Prescribe adrenaline
• Systemic cold exposure can induce anaphylaxis
• History of cold-induced anaphylaxis, history of angioedema
• Desensitization: repeated cold exposure to reduce skin sensitivity to cold

• Greater dosages of non-sedating
second-generation H1-antihistamine
were more effective than standard
dosages in cotrolling cold urticaria
without higer adverse events
• Omalizumab at 150 and 300 mg every
4 weeks was shown to be effective
second-generation H1-antihistamine
Updosing antihistamine
Omalizumab
Kulthanan K, et al. JACI 2019 Apr 1;143(4):1311-31.

Physical urticaria: Heat urticaria
•Very rare
•Induced by local heating of skin at 38-44 oC
•Clinical manifestation
• Symptoms develop several minutes after exposure
•Diagnosis
• Challenge test: application of hot water in tube or beaker at up 44 oC for 4-5
minutes or TempTest
•Treatment: antihistamine only limited value

Physical urticaria: solar urticaria
• 1% of all patients, slight female predominance
• Associated with erythropoietic porphyria
• Depend on wavelength, intensity, duration of irradiation
• Wheals caused by electromagnetic wavelength 290-760 nm (UVB, UVA, visible spectrum)
• Short exposures induce flare and pruritus, longer exposures induce wheal
• Urticaria developed within minutes or hours after sun exposure
• Fade within 24 hours after cessation of exposure
• Lesions usually confined to sun-exposed skin, can develop under clothing

Physical urticaria: solar urticaria
•Diagnosis: photo-testing
•Treatment
• Antihistamine
• Sun avoidance
• High sun protection factor (SPF)
• Protective clothing
• Protective window shields
• Limit time spent outdoors

Non-physical urticaria: cholinergic urticaria
• Second most common physical urticaria
• Occur mainly in adolescents, young adults, patients with atopy
• Rash triggered by activation of cholinergic sympathetic innervation of
sweat glands
• Highly pruritic pinpoint pale wheals 1-3 mm. surrounded by red flare
• Usually begin on trunk and neck, extending outward face and limbs
• Wheal occur anywhere except soles and palms
• Angioedema and anaphylaxis in severely affected patients
• Follow a rise in core temperature resulting from physical exercise,
fever, external passive heat Maurer M, et al. JACI in practice 2018 Jul 1;6(4):1119-30.

Exercised-induced anaphylaxis cholinergic urticaria
Non-physical
induced urticaria
Anaphylactic reaction induced by physical
activity only, food or drug dependent
Passive heating (hot baths,
showers) is common trigger for
cholineric urticaria
Typical lesions • Skin symptoms start with distal pruritis
(palmar, plantar, ears)
• Followed by flushing and erythematous or
urticarial rash with larger lesion
• Start with small wheals
• Then converge into larger
lesion
Atopic background Atopic disposition esp. patients
with early onset of disease

• Diagnosis:
• Provocation testing and rule out exercise-induced anaphylaxis
• Exercise or passive heating in a hot bath at up to 42 oC for 15 minutes
• Treatment
• Avoidance of overheating is essential, but almost impossible
• Non-sedating second-generation antihistamine
• Beta-blockers, danazol, ketotifen and montelukast
• Refractory for up to 24 hours
• Desensitization protocol: regular physical exercise or treatment with autologous sweat
benefit in some patients
• Prognosis: favorable but 30% of patients affected for over 10 years Clinical Immunology 5th edition

Non-physical urticaria: aquagenic urticaria
• Very rare, occur in women > men
• Triggered by water contact but not after drinking water
• Scattered small papular wheals, similar to cholinergic
urticaria but with larger flare
• Appear within 10-20 minutes of water contact
• Resolve in 30-60 minutes
• Associated with HIV and hepatitis B infection
• Diagnosis: water compress at 35 oC applied to skin in the
upper body for 30 minutes

Non-physical urticaria: contact urticaria
• Occur locally after skin or mucosal contact with eliciting agent
• Reaction developed within a few minutes and resolve over 2 hours
• Delayed-contact urticaria can occur with latent period up to 48 hours
• 15% of patients, contact with allergen may induce anaphylaxis
• Caused by organic and inorganic stimuli, mainly in atopic subjects
• Most common = foods
• latex, animal danders, foods, plants, topical drug and cosmetics
• Severity depends on area of exposure, duration of contact, amount,
concentration of substance, patient reactivity, comorbidity, concomitant treatment
• Nonallergic contact urticaria: more common

Diagnostic approach
•History
•Physical examination
•Laboratory assessments
• No definitive diagnostic tests for urticaria
• Evaluation relies on history and physical
examination

History
• Time of onset of disease
• Shape, size, frequency, duration and distribution
• Associated angioedema
• Associated symptoms: bone/joint pain, fever, abdominal cramps
• Induction by physical agents or exercise
• Occurrence in relation to
• Daytime, weekends, menstrual cycle, holidays and foreign travel
• Foods and drugs (NSAIDs, ACE inhibitors)
• Infection, stress

History
•Previous or current allergic disease
•Underlying disease: infection, autoimmune disease, gastrointestinal problems
•Social and occupational history
•Previous therapy and response to therapy: dosage and duration
•Family and personal history of wheals and angioedema

Red flags
•Angioedema: swelling of face, lips, tongue
•Stridor, wheezing or other respiratory distress
•Hyperpigmented lesions, ulcers or urticaria persist > 48 hours
•Signs of systemic illness: fever, lymphadenopathy, jaundice, weight loss

Laboratory assessment
•No routine diagnostic test, unless patient history is strongly suggestive in
acute urticaria
•Only exception is suspicion of acute urticaria due to type I food allergy in
sensitized patients or existence of other eliciting factors: NSAIDs
• Allergic testing allow patients to avoid re-exposure to relevant causative factors
• Skin prick test, specific IgE

Laboratory assessment

Dissociation between history and challenge in physical urticaria
Prospective cohort of 76 subjects aged 3-
77 years, diagnosed with physical-induced
urticaria by internist, pediatrician, allergist
or dermatologist
Challenge testing toward
presenting diagnosis
Komarow HD, et al. JACI in practice 2014 Nov 1;2(6):786-90.

Dissociation between history and challenge in physical urticaria
• 38% challenge negative to presenting diagnosis
• 28% remained negative to all challenge testing
• Diagnosis by history, verified by testing, if possible,
to proper lifestyle modification and pharmacologic
intervention
Less likely negative challenge in
cold urticaria, delayed pressure
urticaria and dermatographism
Komarow HD, et al. JACI in practice 2014 Nov 1;2(6):786-90.

Prevalence of CIndU
• Multicenter, prospective, descriptice
study 2013-2014
• 245 patients with CSU and 127 controls
• 75.9% reported physical trigger, only
36.3% had positive results
• Physical triggers must be verified by
challenge test to avoid unnessary
lifestyle restrictions
Sánchez J, et al. The Journal of Allergy and Clinical Immunology: In Practice. 2017 Mar 1;5(2):464-70.

Differential diagnosis

Differential diagnosis
Urticaria Angioedema
• Urticarial vasculitis
• Mastocytosis
• Acquired autoinflammatory disorder
• Schnitzler’s syndrome
• Systemic-onset juvenile idiopathic arthritis (sJIA)
• Adult-onset Still’s disease
• Hereditary autoinflammatory disorder
• Cryopyrin associated periodic syndrome (CAPS)
• Familial cold auto-inflammatory syndrome (FCAS)
• Muckle-Wells syndrome (MWS)
• Neonatal onset multisystem inflammatory disease (NOMID)
• HyperIgD syndrome (HIDS)
• TNF receptor alpha-associated periodic syndrome (TRAPS)
• Hereditary angioedema (HAE)
• Acquired angioedema due to C1-inhibitor
• Angiotensin converting enzyme (ACE)
inhibitor induced angioedema
Davis MD, et al. JACI in practice 2018 Jul 1;6(4):1162-70.

Urticarial vasculitis
•Prevalence 5% chronic
idiopathic urticaria
•Female predominant
•Peak 4th decade

Cutaneous features of urticarial vasculitis
• Painful lesion, tender, burning, pruritus
• Duration of lesion: 24-72 hours (last longer
than 24 hours)
• Lesion may resolve with purpura or
hyperpigmentation
• Less common: erythema multiforme, livedo
reticularis, Raynaud’s phenomenon

• Accompanying signs and symptoms
• Fever, arthritis, arthralgia, weight change, bone pain,
lymphadenopathy
• Skin-limited or features of systemic disorder
• Sjögren syndrome, SLE
• Diagnosis
• Biopsy is needed for confirmation of diagnosis
• Leukocytoclastic vasculitis
• ANA, RF, C3, C4, C1q, inflammatory markers
• Hypocomplement = more severe nature
• Treatment
• Antihistamine: pruritus
• Dapsone, colchicine, HCQ, indomethacin,
corticosteroid,azathioprine, methotrexate

Mastocytosis
• Overproliferation and accumulation of
tissue mast cells
• Skin involvement
• Most common = urticarial pigmentosa
(UP), maculopapular cutaneous
mastocytosis (MPCM)
• Darier sign: rubbing of lesions lead
to urtication and erythema over and
around macules

Mastocytosis • Similar clinical features
• Skin, GI tract, liver, spleen, bone marrow and skeletal system
• Respiratory, endocrine, renal system rare
• Flushing, hypotension provoked by alcohol, aspirin, insect
stings, infection, exposure to iodinated contrast materials

Schnitzler syndrome
• Rare condition in fifth decade of life
• Skin manifestation
• Chronic recurrent and nonpruritus discrete and confluent plaques
• Typical 0.5 to 3 cm diameter
• Persist for up to 24 hours, resolve without residual pigmentation
• Do not respond to antihistamine
• Accompanied by fever, arthralgia, arthritis, bone pain, lymphadenopathy,
hepatosplenomegaly, leukocytosis, elevated acute phase protein
• Presence of monoclonal paraproteinemia, typically IgM
• Less common IgG, variant Schnitzler

Systemic autoinflammatory disorders
Cryopyrin-Associated Periodic Syndromes (CAPS) HIDS TRAPS Schnitzler
FCAS MWS NOMID
Gene NLRP3 NLRP3 NLRP3 MVK TNFRSF1A Currently unknown
Inheritance AD AD AD AR AD Unknown
Timing • 12-24 hours
• 1-3 hours after exposure
to cold
• Last 203 days
• Random onset-
flares
• Triggered by cold
Continuous with
increase symptoms
and fever during flares
• 3-7 days
• Every 2-12 weeks
• Occur after
vaccination
• Days to weeks
• Average flares 3
weeks
• 12-36 hours
• Rash first,
intermittent fever
occur seperately
from rash
Age of onset Infancy Infanct Neonatal/early infancy >90% infancy First attack by 3
years, all begin by 20
years
Middle age, over 35-
50 years

Cryopyrin-Associated Periodic Syndromes (CAPS) HIDS TRAPS Schnitzler
FCAS MWS NOMID
Skin Cold induced urticaria Cold induced urticaria Ever-present
Urticaria-like rash
Diffuse MP rash,
apthous ulcers
Migrating rash with deep
pain
MP rash and plaques
Neurologic Headache after cold
exposure
Headache after cold
exposure
• Headache
• Chronic aseptic
meningitis
Headache Some headache Fatigue and headache
Auditory Mild hearing loss SNHL, adolescent SNHL, infancy Uncommon Uncommon Uncommon
Ophthalmic Conjunctivitis Conjunctivitis Papilledema, uveitis,
conjunctivitis
Uncommon Conjunctivitis -
Cardiopulmonary - Rare Pericardial effusion Rare, infection pleurisy -
Abdomen Uncommon Somw abdominal pain N/V, abdominal pain Extreme pain, N/V Pertitonitis, diarrhea Hepatosplenomegaly
Joints Arthralgia Arthralgia Joint pain, deformity Arthralgia Intermittent or chronic
arthritis
80% muslce, bone ,
joint pain
Vasculitis - - Rare Cutaneous
vasculitis
HSP 20% vasculitis
Amyloidosis Some >25% <2% <5-10% 10-20% Few patients
Abnormal labs High ESR, CRP, SAA,
leukocytosis
High ESR, CRP, SAA,
leukocytosis
Chronically high ESR,
CRP, SAA, anemia
leukocytosis
High ESR, CRP,
SAA, leukocytosis,
high IgD/IgA
High ESR, CRP, SAA,
leukocytosis, polygonal
gammopathy
Monoclonal IgM, IgG
gammopathy

Treatment
•Patient education
•Identification and elimination of underlying causes
•Avoidance of eliciting factors
•Prevention and care for dry skin
•Avoid skin stimulation
•Pharmacological treatment to prevent mast cell mediator release

Pharmacological treatment
•Antihistamine
•Alternative treatment
•Corticosteroid
•Combination of H1 and H2-antihistamine
•Leukotriene receptor antagonist
•Ciclosporin
•Omalizumab

Treatment

Antihistamine
•Non-sedating second-generation antihistamines are preferable
• Increasing dose up to 4-fold of evidence-based drugs increase efficacy without
increasing adverse effects
• Levocetirizine, desloratadine, rupatadine, bliastine
• Fexofenadine, no randomized controlled trial data
• If unable to sleep, sedating first-generation antihistamine may be beneficial for
short period

Antihistamine 2nd generation
Drug Age approved Dosage Interval Dose adjustment Pregnancy category Cost (Baht)
Cetirizine US >6 mo.
(Thai >2 yr.)
6mo-2yr: 2.5 mg OD
2-5yr: 2.5 mg OD, q12h
≥6yr: 5-10 mg OD
12-24h Renal and hepatic
impairment
B Syrup 1mg/ml: 15.5
Tab 10mg: 1
Levocetirizine >6mo. 6-11mo: 1mg OD
1-5yr: 1.25 mg OD
6-11yr: 2.5 mg OD
>12yr: 5 mg OD
OD Renal and hepatic
impairment
(not hepatic only)
B Tab 5mg: 3.25, 12.5
loratadine >2yr. 2-5yr: 5 mg OD
≥6yr: 10 mg OD
OD Hepatic
impairment
B Syrup 5mg/5ml: 146
Tab 10mg: 1.5, 10.5
Desloratiadine US >6mo.
(Thai >2yr)
6-11mo: 1 mg OD
1-5yr: 1.25 mg OD
6-11yr: 2.5 mg OD
>12yr: 5 mg OD
OD Renal impairment C Syrup 2.5mg/5ml: 160
Tab 5mg: 5.5, 11.5
แนวทางการดูแลรักษาโรคลมพิษ 2557

Antihistamine 2nd generation
Drug Age approved Dosage Interval Dose adjustment Pregnancy category Cost (Baht)
Fexofenadine > 6mo. 6mo-2yr: 15 mg bid
2-11yr: 30 mg bid
≥12yr: 60mg bid or
180 mg OD
Q12-24h Renal impairment
Fruit juice may reduce
bioavailability
C Susp 6mg/ml: 247
Tab 60mg: 2.75
Tab 180mg: 6.25
Rupitadine US >2yr.
(Thai >6yr.)
2-6yr: 2.5 mg OD
6-11yr: 5 mg OD
OD Renal or heaptic
impairment
B
Bilastine >12yr. 20 mg OD OD No dose adjustment Limited Tab 20mg: 16
แนวทางการดูแลรักษาโรคลมพิษ 2557

High dose desloratadine in cold urticaria
• Prospective, double-blind, randomized,
placebo-controlled crossover study
• Patients aged 18-75 years with acquired
cold urticaria ≥ 6 weeks
• 5 mg desloratadine
• 20 mg desloratadine
• Placebo
Cold provocation with TempTest
• Urticarial reaction, critical temperature
threshold, critical stimulation time threshold
• Adverse events
7 days
4-fold-updosing significantly reduced lesion than
standard dose without increase adverse events
Siebenhaar F, et al. JACI 2009 Mar 1;123(3):672-9.

Effectiveness of levocetirizine and
desloratadine in up to 4 times conventional
doses in difficult-to-treat urticaria
• Double-blinded, randomized, 2-parallel-armed trial
• 80 patients aged 19-67 years with difficult-to-treat chronic urticaria
Levocetirizine VS desloratadine
• Start conventional dose 5 mg
• Increase weekly to 10 mg, 20 mg
• Or 20 mg of opposite drug if incomplete
relief of symptoms
Increasing dosage of levocetirizine and desloratadine
up to 4-fold improve chronic urticaria symptoms
without adverse events in difficult-to-treat urticaria
Staevska M, et al. JACI 2010 Mar 1;125(3):676-82.

•Antihistamine
•Corticosteroid
•Combination of H1 and H2-
antihistamine
•Ciclosporin
•Omalizumab
Corticosteroid
• Short course 3-5 days only for severe
episodes of urticaria and angioedema,
unresponsive to antihistamine
• May shorten duration of attack and reduce
symptom severity
• Severe acute urticaria, severe serum
sickness, urticarial vasculitis, delayed
pressure urticaria not responsive to other
treatment
• Not likely to be effective in other types

• Low quality evidence, unclear effects
• Improve symptoms better than H1 alone
•Antihistamine
•Corticosteroid
•Combination of H1 and H2-
antihistamine
•Ciclosporin
•Omalizumab

Prognosis
•Most attacks of acute urticaria settle within 2-3 weeks
•More prolonged attacks were associated with having atopic
background, infection, systemic symptoms

Prognosis
21% turn to chronic urticaria
• Prospective study in Thai patients aged > 18 years
with acute urticaria 2006-2007
• Demographic data, etiology, clinical features,
course of disease, treatment and outcome
Kulthanan K, et al. APJAI 2008 Mar 1;26(1):1.

Urticaria part I

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Urticaria part I