chronic idiopathic urticaria part 2: investigation and management
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Chronic idiopathic urticaria part 2: investigation and management Presented by Wat Mitthamsiri, M.D. August23, 2013TRANSCRIPT
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Chronic Idiopathic Urticaria
Episode 2:Gathering information, investigation and management
Wat Mitthamsiri, M.D.Allergy and Clinical Immunology Unit
Department of MedicineKing Chulalongkorn Memorial Hospital
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Outline
• Gathering information– History– Remarkable notes about PE– Assessment
• Recommended investigations• Management in general
population• Management in special population
(children and pregnant woman
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Gathering information
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History taking
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History taking• Time of onset of disease• Frequency and duration of wheals• Diurnal variation• Occurrence in relation to weekends,
holidays, and foreign travel• Shape, size, and distribution of
wheals• Associated angioedema• Associated subjective symptoms of
lesion, e.g. itch, painTorsten Z, A Summary of the New International EAACI/GA2LEN/EDF/WAO Guidelines in Urticaria, WAO Journal 2012; 5:S1–S5 .
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History taking• Family+personal Hx of urticaria &
atopy• Previous or current allergies,
infections, internal diseases, or other possible causes
• Psychosomatic/psychiatric diseases• Surgical implantations and events
during surgery• Gastric/intestinal problems (stool,
flatulence)• Induction by physical agents or
exerciseTorsten Z, A Summary of the New International EAACI/GA2LEN/EDF/WAO Guidelines in Urticaria, WAO Journal 2012; 5:S1–S5 .
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History taking• Use of drugs– NSAIDs– Injections– Immunizations– Hormones– Laxatives– Suppositories– Ear and eye drops– Alternative remedies
Torsten Z, A Summary of the New International EAACI/GA2LEN/EDF/WAO Guidelines in Urticaria, WAO Journal 2012; 5:S1–S5 .
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History taking• Observed correlation to food• Relationship to the menstrual cycle• Smoking habits• Type of work• Hobbies• Stress• Quality of life related to urticaria
and emotional impact• Previous Rx and response to Rx
Torsten Z, A Summary of the New International EAACI/GA2LEN/EDF/WAO Guidelines in Urticaria, WAO Journal 2012; 5:S1–S5 .
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History taking
EAACI/GA2LEN/EDF/WAO guideline: definition, classification and diagnosis of urticaria, Allergy 2009: 64: 1417–1426.
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Muckle–Wells syndrome• A rare autosomal dominant disease • Comprises of– Sensorineural deafness– Recurrent hives– Amyloidosis
• Other possible symptoms: episodic fever, chills, and painful joints.
• Caused by a defect in the CIAS1 gene which creates the protein cryopyrin
Mukle T, et al., Q J Med. 1962 Apr;31:235-48.Lieberman A. et al., J Am Acad Dermatol. 1998 Aug;39(2 Pt 1):290-1.
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Schnitzler Syndrome• Characteristics– Chronic urticaria– Intermittent fever– Osteosclerotic bone lesions–Monoclonal gammopathy
• Sometimes also: joint pain/inflammation, weight loss, malaise, fatigue, swollen lymph nodess and hepato/splenomegaly
• Unknown causeOren S, et al., IMAJ 2002;4:466±467
Koning H, et al., Seminars in arthritis and rheumatism 37, 2007, (3): 137–48.
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Gleich's Syndrome• A rare disease with– Angioedema– Increased IgM Ab– Eosinophilia
• First described in 1984• Unknown cause
Gleich G, et al., N Engl J Med. 1984 Jun 21;310(25):1621-6.
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Wells Syndrome• A rare disease with pruritic or
tender cellulitis-like eruption• Typical histologic features: – Edema– Flame figures–Marked eosinophils infiltration in the
dermis
• Unknown cause
Wells G, et al., Trans St Johns Hosp Dermatol Soc. 1971;57(1):46-56Brehmer-Andersson E, et al. Acta Derm Venereol. 1986;66(3):213-9.
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History taking
Michihiro H. et al., Japanese Guidelines for Diagnosis and Treatment of Urticaria in Comparison with Other Countries, Allergology International. 2012;61:517-527
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History taking
Michihiro H. et al., Japanese Guidelines for Diagnosis and Treatment of Urticaria in Comparison with Other Countries, Allergology International. 2012;61:517-527
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Physical examination
Remarkable note:• Test for dermographism where
indicated by history
• Antihistamine should be discontinued for at least 2–3 days
EAACI/GA2LEN/EDF/WAO guideline: definition, classification and diagnosis of urticaria, Allergy 2009: 64: 1417–1426.
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Assessment• Disease activity assessment– Urticaria activity score
• Effects on patient’s quality of life– Health Related Quality of Life (HRQL)• General HRQL• Disease-specific HRQL: Chronic Urticaria
Quality of Life Questionnaire (CU-Q2oL)
EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443.
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Assessment
EAACI/GA2LEN/EDF/WAO guideline: definition, classification and diagnosis of urticaria, Allergy 2009: 64: 1417–1426.
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Assessment: Japanese
Michihiro H. et al., Japanese Guidelines for Diagnosis and Treatment of Urticaria in Comparison with Other Countries, Allergology International. 2012;61:517-527
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HRQL
Centers for Disease Control and Prevention. Measuring Healthy Days. Atlanta, Georgia: CDC, November 2000.
• http://www.cdc.gov/hrqol/hrqol14_measure.htm
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HRQL
Murphy B, et al. Australian WHOQoL instruments: User’s manual and interpretation guide. World Health Organization (1993).WHOQoL Study Protocol. WHO (MNH7PSF/93.9).
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CU-Q2oL
Baiardini I, et al. Allergy. 2005 Aug;60(8):1073-8.
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CU-Q2oL
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CU-Q2oL
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CU-Q2oL
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Recommended investigation
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Recommended Tests
Torsten Z, A Summary of the New International EAACI/GA2LEN/EDF/WAO Guidelines in Urticaria, WAO Journal 2012; 5:S1–S5 .
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Recommended Tests
Torsten Z, A Summary of the New International EAACI/GA2LEN/EDF/WAO Guidelines in Urticaria, WAO Journal 2012; 5:S1–S5 .
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Recommended Tests
Torsten Z, A Summary of the New International EAACI/GA2LEN/EDF/WAO Guidelines in Urticaria, WAO Journal 2012; 5:S1–S5 .
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Recommended Tests
Torsten Z, A Summary of the New International EAACI/GA2LEN/EDF/WAO Guidelines in Urticaria, WAO Journal 2012; 5:S1–S5 .
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Infection
• H. pylori• Streptococci• Staphylococci• Yersinia• Giardia lamblia• Mycoplasma pneumonia
EAACI/GA2LEN/EDF/WAO guideline: definition, classification and diagnosis of urticaria, Allergy 2009: 64: 1417–1426.
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Infection
• Hepatitis virus• Norovirus• Parvovirus B19• Anisakis simplex• Entamoeba spp• Blastocystis spp• Dental or ENT infections
EAACI/GA2LEN/EDF/WAO guideline: definition, classification and diagnosis of urticaria, Allergy 2009: 64: 1417–1426.
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Infection
• Hepatitis virus• Norovirus• Parvovirus B19• Anisakis simplex• Entamoeba spp• Blastocystis spp• Dental or ENT infections
EAACI/GA2LEN/EDF/WAO guideline: definition, classification and diagnosis of urticaria, Allergy 2009: 64: 1417–1426.
•Norwalk virus•Feco-oral and contact transmission•Most common cause of viral gastroenteritis in humans•Affect people of all ages
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Infection
• Hepatitis virus• Norovirus• Parvovirus B19• Anisakis simplex• Entamoeba spp• Blastocystis spp• Dental or ENT infections
EAACI/GA2LEN/EDF/WAO guideline: definition, classification and diagnosis of urticaria, Allergy 2009: 64: 1417–1426.
•Fifth disease (Slapped cheek syndrome)•Anemia in AIDS•Reactive arthritis•Hydrop fetalis•Aplastic crisis
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Infection
• Hepatitis virus• Norovirus• Parvovirus B19• Anisakis simplex• Entamoeba spp• Blastocystis spp• Dental or ENT infections
EAACI/GA2LEN/EDF/WAO guideline: definition, classification and diagnosis of urticaria, Allergy 2009: 64: 1417–1426.
•Nematodes parasite•Host: fish and marine mammals
•possible cause of recurrent acute spontaneous urticaria
Foti C, et al. Acta Derm Venereol 2002;82:121–123
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Infection
• Hepatitis virus• Norovirus• Parvovirus B19• Anisakis simplex• Entamoeba spp• Blastocystis spp• Dental or ENT infections
EAACI/GA2LEN/EDF/WAO guideline: definition, classification and diagnosis of urticaria, Allergy 2009: 64: 1417–1426.
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Malignancy?
• No longer suggested• No evidence available for a
correlation of urticaria with neoplastic diseases
EAACI/GA2LEN/EDF/WAO guideline: definition, classification and diagnosis of urticaria, Allergy 2009: 64: 1417–1426.
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Thyroid diseases
• Autoimmune hypothyroidism (Hashimoto’s thyroiditis)– Association found with the presence
of peroxidase or thyroglobulin Ab. – Incidence: 12–14%
– 24% incidence of antithyroglobulin Ab or antimicrosomal Ab or both, found in patients with chronic urticaria Kikuchi Y, et al. J Allergy Clin Immunol 2003; 112(1):218.
Leznoff A, et al. Arch Dermatol 1983; 119(8):636–640.Leznoff A, et al. J Allergy Clin Immunol 1989; 84(1):66–71.
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Thyroid diseases
• Autoimmune hypothyroidism (Hashimoto’s thyroiditis)But…– Thyroid status did not relate to the
occurrence of urticaria– Hives persist even with euthyroid
achievement
Allen P Kaplan, Middleton’s Allergy: Principles and Practice 7th edition, 2009: 1063-1081.
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Thyroid diseases
• A case-controlled study (140 vs 181) found that CIU was associated with
• Hashimoto’s thyroiditis > Graves’ disease
• Female > male
Filliz C. et al., Eur J Dermatol 2006; 16 (4): 402-5
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Thyroid diseases• A study trying to figure out the
pathophysiologic relationship of anti-thyroid and anti-FceRIa Ab reported negative finding:– Incubation of patient sera with FceRIa:
decreased ability to detect anti-FceRIa Ab
– But not thyroglobulin or thyroid peroxidase
– Incubation with thyroid antigens did not activation of mast cells
Jonathan DM., et al. Journal of Investigative Dermatology (2010) 130, 1860–1865.
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Thyroid diseases
• So…epitopic cross-reactivity does not explain the increased prevalence of Hashimoto’s thyroiditis in CIU patients
• The frequent concurrence of Hashimoto’s thyroiditis and CIU likely reflects a genetic tendency toward autoimmune diseases
Jonathan DM., et al. Journal of Investigative Dermatology (2010) 130, 1860–1865.
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Thyroid diseases
• A recent case-controlled study of 115 patient found that– Patients with CIU and autoimmune
thyroid disease had greater risk of angioedema (16.2 times)
• Odds ratio– Hypothyroidism: 4.6 (CI = 1.00-21.54) – Hyperthyroidism: 3.3 (CI = 0.38-
28.36).
Ruy FBGM., et al., Sao Paulo Med J. 2012; 130(5):294-8
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Other autoantibodies
• Autologous Serum Skin Test (ASST)
• in vitro histamine release from basophils: Histamine releasing assay
EAACI/GA2LEN/EDF/WAO guideline: definition, classification and diagnosis of urticaria, Allergy 2009: 64: 1417–1426.
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ASST• In-vivo test detecting functional
autoantibody• Sensitivity about 70%• Specificity about 80%
• Positive in about 40% of CIU patients (30-50% in previous literature)
M Abd El-Azim, et al., J Investig Allergol Clin Immunol 2011; Vol. 21(7): 546-550
Sabroe R., et al. J Am Acad Dermatol. 1999;40:443-50.
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ASST• A small report found that positive
ASST patients tend to have– Less inflammatory process than the
ASST negative patient• Less TNF-alpha• Less chemokines • Less expression of adhesion molecules
• ASST negative patients might be more refractory to Rx
Stefania P., et al., Int Arch Allergy Immunol 2002;128:59–66
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ASST• But newer study reported that
patients with ASST positive tend to have:–More frequent urticaria attacks– Higher urticaria activity score– Lower absolute eosinophil count– Lower serum IgE titer– Significantly higher antithyroid Ab
titer– Significantly higher B-cell
percentage M Abd El-Azim, et al., J Investig Allergol Clin Immunol 2011; Vol. 21(7): 546-550
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ASST• Another report found that patients
with positive ASST…– No significantly different clinical
variables:• Disease severity, duration, attack frequency• Presence of angioedema • Family history of urticaria • Family/personal history of atopy• Family/personal history of autoimmune (eg.
thyroid disease, DM, vitiligo, and rheumatoid)
– Significantly associated with distribution of wheals on the face and extremities
Hayder R. ISRN Dermatology Volume 2013, Article ID 291524, 4
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ASST in Thai• Only 1 study of 85 patient during
2002-2003– 24.7% of patients had a positive ASST
• There was no significant difference between patients with positive ASST and negative ASST in these variables:– Severity (wheal no., wheal size, itching
scores and body area involvement)– Duration of the diseaseKanokvalai K. et al., Asian Pac J Allergy Immunol. 2006 Dec;24(4):201-6.
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ASST: Teniques
• ID injection of 50 μL at volar forearm of:– Autologous serum– histamine – Sterile physiological saline
• Avoid areas known to have had spontaneous wheals in previous 48 hours–Mast cells may be refractory to further
activation (local tachyphylaxis)M Abd El-Azim, et al., J Investig Allergol Clin Immunol 2011; Vol. 21(7): 546-550
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ASST: Teniques
• Measure the wheal after 30 minutes (15 minutes for histamine)– At its 2 longest perpendicular
diameters – Calculate the average value
• A positive ASST result was defined as: – Serum-induced wheal diameter was
larger than saline-induced wheal diameter ≥1.5 mm, at 30 minutesM Abd El-Azim, et al., J Investig Allergol Clin Immunol 2011; Vol. 21(7): 546-550
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Histamine releasing assay
• Gold standard of detecting functional autoantibodies
• Time-consuming procedure• Difficult to standardize• Requires fresh basophils from
healthy donors
Grattan CE, et al. J Am Acad Dermatol. 2002;46:645-57,
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Other tests
• Blood basophil count• Skin biopsy
• Skin biopsy– Histologic pattern does not correlate
with the severity of urticaria– And can’t be used as a guide to Rx
EAACI/GA2LEN/EDF/WAO guideline: definition, classification and diagnosis of urticaria, Allergy 2009: 64: 1417–1426.
Allen P Kaplan, Middleton’s Allergy: Principles and Practice 7th edition, 2009: 1063-1081.
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Other tests
D-dimer: There are reports about• Positive autologus plasma skin
testing (APST) is higher than that of positive autologus serum skin testing (ASST) (80% vs. 50%)
• This difference suggested that coagulation cascade is possibly involved in the pathogenesis of CIU
Asero R, et al., J Allergy Clin Immunol 2006;117:1113-7.
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Other tests
D-dimer: There are reports about• Increased level of D-dimer in
chronic urticaria patient– 10-35% in previous study– 48.3% in a Thai study
• Positive correlation between plasma D-dimer level and disease severity
Daranporn T. Asia Pac Allergy 2013;3:100-105.
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Other tests
D-dimer: There are reports about• No statistically significant
difference in plasma D-dimer level between:– APST positive and negative groups– ASST positive and negative groups.
• This may be an alternative way to evaluate disease severity in patients with CIU
Daranporn T. Asia Pac Allergy 2013;3:100-105.
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Other tests
• There are potential tests that may be useful in the future
• But they still need to be validated–Western blotting– ELISA– Flow cytometry using chimeric cell
lines expressing the human FcεRIα
Grattan CE, et al., J Am Acad Dermatol 2002; 46: 645-57; quiz 57-60
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In Japanese guideline
Michihiro H. et al., Japanese Guidelines for Diagnosis and Treatment of Urticaria in Comparison with Other Countries, Allergology International. 2012;61:517-527
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In Japanese guideline
Michihiro H. et al., Japanese Guidelines for Diagnosis and Treatment of Urticaria in Comparison with Other Countries, Allergology International. 2012;61:517-527
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In Japanese guideline
Michihiro H. et al., Japanese Guidelines for Diagnosis and Treatment of Urticaria in Comparison with Other Countries, Allergology International. 2012;61:517-527
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Managementin
General Population
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General Principle
• Specific Rx
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General Principle
• Specific Rx = Remove cause
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General Principle
• Specific Rx = Remove cause
•Cause???
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General Principle
• Specific Rx = Remove cause
•Cause???
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General Principle
• Specific Rx = Remove cause
•Cause???
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General Principle
• Specific Rx = Remove cause
•Cause???
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General Principle
• All we can do now is just symptomatic Rx
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General Principle
• All we can do now is just symptomatic Rx
อย่�างน้�อย่ก็ย่งดี�ก็ว่�า
รัก็ษาไม่�ไดี�น้ะครับ
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Goal of Rx
• 1st stage: Symptom free
Michihiro H. et al., Japanese Guidelines for Diagnosis and Treatment of Urticaria in Comparison with Other Countries, Allergology International. 2012;61:517-527
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Goal of Rx
• 1st stage: Symptom free• Final stage: Drug free
Michihiro H. et al., Japanese Guidelines for Diagnosis and Treatment of Urticaria in Comparison with Other Countries, Allergology International. 2012;61:517-527
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recommendations
EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443.
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recommendations
EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443.
• Low cost• Very good safety profile
• Very good evidence of efficacy
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recommendations
EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443.
2nd Generation = 1st Line•Cetirizine•Desloratadine•Fexofenadine•Levocetirizine•Acrivastine•Ebastine•Mizolastine
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recommendations
EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443.
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recommendations
EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443.
• Low cost• Good safety profile
• Good evidence of efficacy
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recommendations
EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443.
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recommendations
EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443.
• Low/medium low cost• Good safety profile
• Insufficient evidence of efficacy
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recommendations
EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443.
Patients with cellular infiltration•May be refractory to antihistamines•May respond completely to a brief burst of corticosteroid
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recommendations
EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443.
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recommendations
EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443.
•Medium to high cost•Moderate safety profile•Moderate level of evidence for efficacy•Recommended only for patients with severe disease refractory to antihistamine•Far better risk/benefit ratio compared with steroids.
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recommendations
EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443.
•Moderate, direct effect on mast cell mediator release •Only agent to inhibit basophil histamine release
Zuberbier T, et al. Acta Derm Venereol 1996;76:295–297.
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recommendations
EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443.
•Low cost•Good safety profile•Very low level of evidence for efficacy
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recommendations
EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443.
•Low cost•Medium level of side effects•Low level of evidence for efficacy
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recommendations
EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443.
•High cost•Good safety profile•Low level of evidence for efficacy
•Dramatically effective in selected patient Spector SL, et al., Ann Allergy Asthma Immunol 2007;99:190–193
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recommendations
• There is a strong recommendation against the long-term use of corticosteroids outside specialist clinics
• If there is no special indication, we recommend against the routine use of old sedating first generation antihistamines
EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443.
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recommendations
• We recommend against the use of astemizole and terfenadine– Pro-drugs requiring hepatic
metabolism to become fully active– Cardiotoxic if this metabolism was
blocked by concomitant administration of ketoconazole or erythromycin
EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443.
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recommendations• Suggest the same first line
treatment and up-dosing for children (weight adjusted)
• Suggest the same first line treatment in pregnant or lactating women– (but safety data in a large meta-
analysis is limited to loratadine)
EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443.
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EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443.
Autoantibody reduction
• Plasmapheresis– Benefit in severely affected patients– High costs– AutoAb-positive patients who are
unresponsive to all other treatment.
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EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443.
Autoantibody reduction
• Immunomodulatory Rx:– Intravenous immunoglobulins (IVIG)–Methotrexate– Azathioprine–Mycophenolate mofetil– Cyclophosphamide– Anti-IgE (Omalizumab)– Tacrolimus
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EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443.Hannuksela M, et al., Acta Derm Venereol 1985;65:449–450.
Borzova E, et al., J Am Acad Dermatol 2008;59:752–757.
Other Rx
• Phototherapy– UV-A and UV-B Rx for 1–3 months
can be added to antihistamine treatment
• These agents were just case reports and only be used in large centers as last options
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EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443.
Other Rx: Combinations
• Nonsedating H1-antihistamines with:– Stanazolol–Montelukast– Zafirlukast–Mycophenolate mofetil– Narrowband UV-B
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EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443.
Other Rx: Monotherapy• There are reports but poor evidence
of…– Ketotifen–Montelukast–Warfarin– Hydroxychloroquine– Oxatomide– Doxepin– Nifedipine– Autologs whole blood Injection
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EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443.
Other Rx
• Monotherapy: Only case-control report, no RCT about…– Dapsone– Sulfasalazine–Methotrexate– Interferon– Plasmapheresis– IVIG
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EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443.
F/U evaluation
• Re-evaluate the necessity for continued or alternative drug treatment every 3–6 months.
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recommendations
EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443.
These agents might be added in some patients•Hydroxyzine or diphenhydramine•Doxepin•Prednisone
Allen P Kaplan, Middleton’s Allergy: Principles and Practice 7th edition, 2009: 1063-1081.
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Adjusting medication
• Sometimes, sedating antihistamine might be needed– Hydroxyzine or diphenhydramine
200mg/day divided into 3 or 4 doses
• Or sometimes, Doxepin– It can interact with H1 receptors – And also possesses some H2
receptor activity
• But beware of sedation
Allen P Kaplan, Middleton’s Allergy: Principles and Practice 7th edition, 2009: 1063-1081.
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Adjusting medication
• Drugs must be taken as prescribed and not just as needed– Daily administration minimizes or
prevents outbreaks– Use of antihistamines after the onset of
lesions occurs is too late– Ratio of histamine vs antihistamine at
the cutaneous endothelial cell H1 receptor determines the response
– If histamine level exceeds antihistamine level, Rx will be ineffective
Allen P Kaplan, Middleton’s Allergy: Principles and Practice 7th edition, 2009: 1063-1081.
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Adjusting steroid
Allen P Kaplan, Middleton’s Allergy: Principles and Practice 7th edition, 2009: 1063-1081.
Day 1 2 3 4 5 6 7Dose (mg) 40 40 40 35 30 25 20
• Start with prednisone 40 mg/d
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Adjusting steroid
Allen P Kaplan, Middleton’s Allergy: Principles and Practice 7th edition, 2009: 1063-1081.
Day 1 2 3 4 5 6 7Dose (mg) 40 40 40 35 30 25 20
• Start with prednisone 40 mg/d
Day 8 9 10 11 12 13 14Dose (mg) 15 20 10 20 5 20 -
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Adjusting steroid
Allen P Kaplan, Middleton’s Allergy: Principles and Practice 7th edition, 2009: 1063-1081.
Day 1 2 3 4 5 6 7Dose (mg) 40 40 40 35 30 25 20
• Start with prednisone 40 mg/d
Day 8 9 10 11 12 13 14Dose (mg) 15 20 10 20 5 20 -
Day 15 16 17 18 19 20 21Dose (mg) 20 - 20 - 20 - 20
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Adjusting steroid
• Then taper steroid dosage by 2.5–5.0 mg every 2-3 weeks
• Nearly 3 months would be needed to discontinue the steroid
• Sometimes, steroid cannot be tapered below a certain dosage– That dosage may be maintained for
1-2 month– Then try tapering again
Allen P Kaplan, Middleton’s Allergy: Principles and Practice 7th edition, 2009: 1063-1081.
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Adjusting steroid
• Common problem– Good control of on the steroid ‘on’ day– Prominent exacerbation on the ‘off’ day
• Solution– Separate prednisone into b.i.d. dosage– After good control, try tapering the
evening dosage first– Or daily dosage might be used
Allen P Kaplan, Middleton’s Allergy: Principles and Practice 7th edition, 2009: 1063-1081.
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Adjusting steroid
• Some patient unable to metabolize prednisone to prednisolone– Low dosage of methylprednisolone is
often effective
• Antihistamines :continued and should not be tapered until steroid is no longer required
Allen P Kaplan, Middleton’s Allergy: Principles and Practice 7th edition, 2009: 1063-1081.
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EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443.
Rx associated condition
• Rx of associated infection• Rx of inflammatory processes– Gastritis– Reflux esophagitis– Inflammation of the bile duct or gall
bladder
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EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443.
Rx associated condition
• Rx of food and drug intolerance– Diet containing only low levels
pseudoallergens : instituted and maintained for at least 3–6 month
– In pseudoallergy, a diet must be maintained for a minimum of 3 weeks before beneficial effects are observed.
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EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443.
Rx associated condition
• Rx psychological factors • Symptomatic relief should be
offered while searching for causes
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EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443.
Unrecommended Rx• Tranexamic acid• Sodium cromoglicate (SCG)• Sedating H1-antihistamine+cimetidine• Sedating H1-antihistamine+terbutaline• Leukotriene antagonist monotherapy–Montelukast– Zafirlukast
• Montelukast+desloratadine• Monotherapy with H2 receptor
antagonist
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In Japanese guideline
Michihiro H. et al., Japanese Guidelines for Diagnosis and Treatment of Urticaria in Comparison with Other Countries, Allergology International. 2012;61:517-527
![Page 110: Chronic idiopathic urticaria part 2: investigation and management](https://reader035.vdocuments.mx/reader035/viewer/2022062307/554b018bb4c905c12d8b4db0/html5/thumbnails/110.jpg)
In Japanese guideline
Michihiro H. et al., Japanese Guidelines for Diagnosis and Treatment of Urticaria in Comparison with Other Countries, Allergology International. 2012;61:517-527
ตัว่หน้งสื�อเล็ก็แบบน้�� จะอ�าน้ออก็ไดี�ไงเน้��ย่???
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In Japanese guideline
Michihiro H. et al., Japanese Guidelines for Diagnosis and Treatment of Urticaria in Comparison with Other Countries, Allergology International. 2012;61:517-527
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In Japanese guideline
Michihiro H. et al., Japanese Guidelines for Diagnosis and Treatment of Urticaria in Comparison with Other Countries, Allergology International. 2012;61:517-527
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In Japanese guideline
Michihiro H. et al., Japanese Guidelines for Diagnosis and Treatment of Urticaria in Comparison with Other Countries, Allergology International. 2012;61:517-527
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In Japanese guideline
Michihiro H. et al., Japanese Guidelines for Diagnosis and Treatment of Urticaria in Comparison with Other Countries, Allergology International. 2012;61:517-527
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Managementin
Special Population
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EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443.
Children
• Same first line treatment and up-dosing (weight adjusted) is recommended as in adults
• But…• Nonsedating H1-antihistamines is
not licensed for use in children <6 months of age
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EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443.
Pregnant woman
General concept:
• Systemic Rx should generally be avoided in pregnant women, especially in the 1st trimester
• But pregnant women have the right to best possible Rx
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EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443.
Pregnant woman
Evidence?• No systematic study on safety of Rx
in pregnant women with urticaria• No study on negative effects of
increased levels of histamine occurring in pregnant woman with urticaria, too.
• No reports of birth defects in women having used 2nd generation antihistamines during pregnancy
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EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443.
Pregnant woman
In real world• 2nd generation antihistamines can
be bought over-the-counter and widely used in self-Rx
• So… many women might have used these drugs at the beginning of pregnancy before the pregnancy was confirmed
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EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443.
Pregnant woman
For highest safety possible, the current suggestion is that:
• Use of 2nd generation antihistamines should be limited to loratadine
• With the possible extrapolation to desloratadine
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Take Home Message
• History is the most important diagnostic tool
• Investigations is for cause searching
• ASST is the best in-vivo test for autoreactivity but basophil histamine release assay is the gold standard
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Take Home Message
• Non-sedating H1-receptor antagonist antihistamine is the 1st line and mainstay of treatment
• Treatment in children use the same principle as normal adult
• In pregnant woman, available data limited only to loratadine
• Other potential agents need more study
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-Thank you-