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Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
Chronic idiopathic urticaria part 2: investigation and management
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Chronic idiopathic urticaria part 2: investigation and management

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Chronic idiopathic urticaria part 2: investigation and management …

Chronic idiopathic urticaria part 2: investigation and management

Presented by Wat Mitthamsiri, M.D.

August23, 2013

Published in: Health & Medicine
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  • 1. Chronic Idiopathic Urticaria Episode 2: Gathering information, investigation and management Wat Mitthamsiri, M.D. Allergy and Clinical Immunology Unit Department of Medicine King Chulalongkorn Memorial Hospital
  • 2. Outline • Gathering information – History – Remarkable notes about PE – Assessment • Recommended investigations • Management in general population • Management in special population (children and pregnant woman
  • 3. Gathering information
  • 4. History taking
  • 5. 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, pain Torsten Z, A Summary of the New International EAACI/GA2LEN/EDF/WAO Guidelines in Urticaria, WAO Journal 2012; 5:S1–S5.
  • 6. 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 exercise Torsten Z, A Summary of the New International EAACI/GA2LEN/EDF/WAO Guidelines in Urticaria, WAO Journal 2012; 5:S1–S5.
  • 7. 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.
  • 8. 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.
  • 9. History taking EAACI/GA2LEN/EDF/WAO guideline: definition, classification and diagnosis of urticaria, Allergy 2009: 64: 1417–1426.
  • 10. 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.
  • 11. 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 cause Oren S, et al., IMAJ 2002;4:466±467 Koning H, et al., Seminars in arthritis and rheumatism 37, 2007, (3): 137–48.
  • 12. 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.
  • 13. 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):46-56 Brehmer-Andersson E, et al. Acta Derm Venereol. 1986;66(3):213-9.
  • 14. 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
  • 15. 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
  • 16. 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.
  • 17. 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.
  • 18. Assessment EAACI/GA2LEN/EDF/WAO guideline: definition, classification and diagnosis of urticaria, Allergy 2009: 64: 1417–1426.
  • 19. 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
  • 20. HRQL Centers for Disease Control and Prevention. Measuring Healthy Days. Atlanta, Georgia: CDC, November 2000. • http://www.cdc.gov/hrqol/hrqol14_measure.htm
  • 21. 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).
  • 22. CU-Q2oL Baiardini I, et al. Allergy. 2005 Aug;60(8):1073-8.
  • 23. CU-Q2oL
  • 24. CU-Q2oL
  • 25. CU-Q2oL
  • 26. Recommended investigation
  • 27. Recommended Tests Torsten Z, A Summary of the New International EAACI/GA2LEN/EDF/WAO Guidelines in Urticaria, WAO Journal 2012; 5:S1–S5.
  • 28. Recommended Tests Torsten Z, A Summary of the New International EAACI/GA2LEN/EDF/WAO Guidelines in Urticaria, WAO Journal 2012; 5:S1–S5.
  • 29. Recommended Tests Torsten Z, A Summary of the New International EAACI/GA2LEN/EDF/WAO Guidelines in Urticaria, WAO Journal 2012; 5:S1–S5.
  • 30. Recommended Tests Torsten Z, A Summary of the New International EAACI/GA2LEN/EDF/WAO Guidelines in Urticaria, WAO Journal 2012; 5:S1–S5.
  • 31. 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.
  • 32. 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.
  • 33. 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
  • 34. 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
  • 35. 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
  • 36. 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.
  • 37. 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.
  • 38. 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.
  • 39. 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.
  • 40. 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
  • 41. 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.
  • 42. 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.
  • 43. 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
  • 44. 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.
  • 45. 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.
  • 46. 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
  • 47. 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
  • 48. 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
  • 49. 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 disease Kanokvalai K. et al., Asian Pac J Allergy Immunol. 2006 Dec;24(4):201-6.
  • 50. 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
  • 51. 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 minutes M Abd El-Azim, et al., J Investig Allergol Clin Immunol 2011; Vol. 21(7): 546-550
  • 52. 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,
  • 53. 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.
  • 54. 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.
  • 55. 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.
  • 56. 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.
  • 57. 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
  • 58. 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
  • 59. 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
  • 60. 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
  • 61. Management in General Population
  • 62. General Principle • Specific Rx
  • 63. General Principle • Specific Rx = Remove cause
  • 64. General Principle • Specific Rx = Remove cause •Cause???
  • 65. General Principle • Specific Rx = Remove cause •Cause???
  • 66. General Principle • Specific Rx = Remove cause •Cause???
  • 67. General Principle • Specific Rx = Remove cause •Cause???
  • 68. General Principle • All we can do now is just symptomatic Rx
  • 69. General Principle • All we can do now is just symptomatic Rx
  • 70. 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
  • 71. 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
  • 72. recommendations EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443.
  • 73. 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
  • 74. 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
  • 75. recommendations EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443.
  • 76. recommendations EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443. •Low cost •Good safety profile •Good evidence of efficacy
  • 77. recommendations EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443.
  • 78. 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
  • 79. 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
  • 80. recommendations EAACI/GA2LEN/EDF/WAO guideline: management of urticaria, Allergy 2009: 64: 1427–1443.
  • 81. 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.
  • 82. 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.
  • 83. 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
  • 84. 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
  • 85. 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
  • 86. 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.
  • 87. 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.
  • 88. 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.
  • 89. 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.
  • 90. 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
  • 91. 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
  • 92. 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
  • 93. 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
  • 94. 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
  • 95. 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.
  • 96. 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.
  • 97. 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.
  • 98. 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.
  • 99. Adjusting steroid Allen P Kaplan, Middleton’s Allergy: Principles and Practice 7th edition, 2009: 1063-1081. Day 1 2 3 4 5 6 7 Dose (mg) 40 40 40 35 30 25 20 • Start with prednisone 40 mg/d
  • 100. Adjusting steroid Allen P Kaplan, Middleton’s Allergy: Principles and Practice 7th edition, 2009: 1063-1081. Day 1 2 3 4 5 6 7 Dose (mg) 40 40 40 35 30 25 20 • Start with prednisone 40 mg/d Day 8 9 10 11 12 13 14 Dose (mg) 15 20 10 20 5 20 -
  • 101. Adjusting steroid Allen P Kaplan, Middleton’s Allergy: Principles and Practice 7th edition, 2009: 1063-1081. Day 1 2 3 4 5 6 7 Dose (mg) 40 40 40 35 30 25 20 • Start with prednisone 40 mg/d Day 8 9 10 11 12 13 14 Dose (mg) 15 20 10 20 5 20 - Day 15 16 17 18 19 20 21 Dose (mg) 20 - 20 - 20 - 20
  • 102. 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.
  • 103. 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.
  • 104. 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.
  • 105. 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
  • 106. 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.
  • 107. 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
  • 108. 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
  • 109. 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
  • 110. 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
  • 111. 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
  • 112. 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
  • 113. 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
  • 114. 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
  • 115. Management in Special Population
  • 116. 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
  • 117. 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
  • 118. 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
  • 119. 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
  • 120. 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
  • 121. 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
  • 122. 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
  • 123. -Thank you-

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