(J Allergy Clin Immunol 2012;129:1307-13)Sadudee (Boonmee) Klakayan, MD
Introduction• Chronic urticaria (CU) : recurrent urticarial lesion  for more than 6 week with symptoms present at  least 3...
Physical urticaria                                Chronic urticaria- Cold urticaria- Cholinergic urticaria- Dermographism-...
• Thyroid disease is the most frequently  investigated disease in association with CIU• Arthur Leznoff et al.  - 17 of 140...
Are autoantibodies present in patient withsubacute and chronic urticaria ?• Survey of autoantibodies in patients with  idi...
• 1 pt. inflammatory bowel disease  1 pt. multiple myeloma  otherwise no other diagnoses of disease  specifically involv...
• Antibodies to thyroid peroxidase (TPO)  common in urticaria 20% vs controls 0%  (p < 0.01)• Rheumatoid factor(RF) increa...
• Conclusion : pt. with urticaria more likely to  have a thyroid autoantibody to TPO or to have  RF• This survey demonstra...
(J Allergy Clin Immunol 2012;129:1307-13)
Objective• Aimed to characterize the association  between CU, autoimmune diseases, and  autoimmune/inflammatory serologic ...
Methods• Maccabi Healthcare Services (MHS) in Israel• Using an automated search on the MHS central  database• Collected da...
• Excluded : physical urticaria, cholinergic urticaria,  dermographism, and urticaria without  specification of ‘‘chronic’...
• For each patient, collected information on  diagnostic history of  - hypothyroidism, hyperthyroidism,  - systemic lupus ...
• Laboratory tests :  - antithyroid peroxidase antibodies  - antithyroglobulin antibodies  - antinuclear antibodies  - rhe...
RESULTS
Study group                                Control group                   Diagnoses of                                 Co...
Thyroid disease and CU
(J Allergy Clin Immunol 2012;129:1307-13)
With in 10 yr(J Allergy Clin Immunol 2012;129:1307-13)
Other autoimmune disease and CU
(J Allergy Clin Immunol 2012;129:1307-13)
With in 10 yr(J Allergy Clin Immunol 2012;129:1307-13)
• few autoimmune diseases were diagnosed during the first 6 monthsafter the diagnosis of CU• most continuously revealed ov...
• OR of pt with CU with additional autoimmune  disease = 17.343 compared with control  (95% CI, 14.222-21.148; P < .0005)•...
Serologic and Labortory markers and CU
Abnormal high306 CU pt.with hypothyroidism have Antithyroid Ab( ATG,ATPO)                                 (J Allergy Clin ...
• Pt. CU group 11,514 pt. with euthyroid   Lab       CU patient   Control   OR               P value             With     ...
Discussion• This study is the first large control study  demonstrating a correlation between CU and  the main autoimmune d...
• Thyroid disease were most common autoimmune  disease accopanying pt with CU  from this study Pt with CU Dx  - hypothyroi...
• Aversano et al hypothesized that inflamatory  status induced by thyroid- stimulating hormone  led to flares of urticaria...
• Rheumatoid arthrits second most common  autoimmune disease in pt. with CU   - 1.9% of female pt. with CU (significant mo...
• Strengths of this study  - large population of pt. with CU  - compared with large match control group  - retrospective s...
Conclusion• Clinical implications:  - CU is probably one of the autoimmune  diseases  - Understanding the disease process ...
• Over the past 2 decades, studies have suggested an  autoimmune mechanism underlying the pathophysiology of  CIU in up to...
Methods• Retrospective analysis patients with an ICD-9 diagnosis  of chronic idiopathic urticaria from October 1, 2007  th...
• Classified into 2 groups: they  - Controlled if they required only H1/H2  antihistamines with or without a leukotriene  ...
• Laboratory data  - ANA  - anti-thyroperoxidase antibody (ATPO)  - anti-thyroglobulin antibody (ATG)  - CU Index (basophi...
Results• Demographic data• All four biomarkers (CU Index, ANA, ATG, ATPO) were measured in 25% ofCIU patients• at least 1 ...
Results• Percentage of patients with positive autoimmune  biomarkers                            Ann Allergy Asthma Immunol...
Results• Autoimmune biomarkers and disease severity                                      80%                              ...
Results• Test characteristics of combinations of autoimmune  biomarkers                                   4.5             ...
Results   Sensitivity, specity,PPV,NPV for identify a          refractory outcome in CIU                                  ...
• Cost of order the autoimmune biomarkers  - ANA= $84.20  - ATG = $128.00  - ATPO= $118.00  - CU Index = $436.00  - combin...
Mediator of hives and swellingMast cell (cutaneous)      Histamine                           Prostaglandin D              ...
Journal club: Chronic urticaria and autoimmunity
Journal club: Chronic urticaria and autoimmunity
Journal club: Chronic urticaria and autoimmunity
Journal club: Chronic urticaria and autoimmunity
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Journal club: Chronic urticaria and autoimmunity

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Journal club: Chronic urticaria and autoimmunity

Presented by Sadudee Boonme, MD. 2012/06/25

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Journal club: Chronic urticaria and autoimmunity

  1. 1. (J Allergy Clin Immunol 2012;129:1307-13)Sadudee (Boonmee) Klakayan, MD
  2. 2. Introduction• Chronic urticaria (CU) : recurrent urticarial lesion for more than 6 week with symptoms present at least 3 times weekly• When the cause is not detected after intensive clinical and laboratory investigation, it is defined as idiopathic• autoimmune mechanisms have been proposed as responsible for the development of some of the cases of chronic idiopathic urticaria (CIU) (J Allergy Clin Immunol 2012;129:1307-13)
  3. 3. Physical urticaria Chronic urticaria- Cold urticaria- Cholinergic urticaria- Dermographism- Pressure urticaria- Solar urticaria Autoimmune chronic Chronic idiopathic-Aquagenic urticaria urticaria urticaria 45% 55%Urticarial vasculitis IgG antiFcεRIα IgG antiIgE subunit 5-10% 35-40%
  4. 4. • Thyroid disease is the most frequently investigated disease in association with CIU• Arthur Leznoff et al. - 17 of 140 cases (12.1%) of chronic urticaria, demonstrated thyroid autoimmunity with thyroid microsomal antibodies (TMAs) ≥ 1: 1600 - 8 of 17 pt. had goiter or thyroid dysfunction - age and sex and thyroid features were similar to pt.with autoimmune thyroiditis - CUA may have an autoimmune basis (Arch Dermatol 1983;119:636-640)
  5. 5. Are autoantibodies present in patient withsubacute and chronic urticaria ?• Survey of autoantibodies in patients with idiopathic subacute and chronic urticaria• 25 pt. vs 75 control (serum tested for autoantibodies)• age 15 to 73 years (mean 48 yr) J Investig Allergol Clin Immunol. 2001;11(1):16-20
  6. 6. • 1 pt. inflammatory bowel disease 1 pt. multiple myeloma otherwise no other diagnoses of disease specifically involving immunity other than atopy• No study patients had diagnosis of autoimmune thyroid disease J Investig Allergol Clin Immunol. 2001;11(1):16-20
  7. 7. • Antibodies to thyroid peroxidase (TPO) common in urticaria 20% vs controls 0% (p < 0.01)• Rheumatoid factor(RF) increased in urticaria 16% vs controls 0% (p < 0.05)• Neither H. pylori antibody nor other autoantibodies were present in significant numbers of urticaria patients compared to controls. J Investig Allergol Clin Immunol. 2001;11(1):16-20
  8. 8. • Conclusion : pt. with urticaria more likely to have a thyroid autoantibody to TPO or to have RF• This survey demonstrates that some markers of autoimmunity (TPO and RF)may be increased in urticaria patients, but other markers of autoimmunity were not found J Investig Allergol Clin Immunol. 2001;11(1):16-20
  9. 9. (J Allergy Clin Immunol 2012;129:1307-13)
  10. 10. Objective• Aimed to characterize the association between CU, autoimmune diseases, and autoimmune/inflammatory serologic markers in a large unselected population (J Allergy Clin Immunol 2012;129:1307-13)
  11. 11. Methods• Maccabi Healthcare Services (MHS) in Israel• Using an automated search on the MHS central database• Collected data on all pt. diagnosis of CU by either allergist and clinical immunology or dermatologist between January 1, 1993, and March 1, 2010 using the ICD-9-CM (J Allergy Clin Immunol 2012;129:1307-13)
  12. 12. • Excluded : physical urticaria, cholinergic urticaria, dermographism, and urticaria without specification of ‘‘chronic’’ have distinct ICD-9-CM• control subjects  pt. who visited - dermatologists - family physicians - allergist not given diagnosis of CU or any other specific disease but were given diagnoses with the ICD-9- CM “ Patient under observation ”• Control subjects matched with cases by age and sex (J Allergy Clin Immunol 2012;129:1307-13)
  13. 13. • For each patient, collected information on diagnostic history of - hypothyroidism, hyperthyroidism, - systemic lupus erythematosus (SLE) - rheumatoid arthritis (RA) - celiac disease - type 1 diabetes mellitus - Sjögren syndrome• The first registration date for each diagnosis was collected (J Allergy Clin Immunol 2012;129:1307-13)
  14. 14. • Laboratory tests : - antithyroid peroxidase antibodies - antithyroglobulin antibodies - antinuclear antibodies - rheumatoid factor - anti–dsDNA antibodies - anticardiolipin antibodies - anti–transglutaminase IgA antibodies - anti–parietal cell antibodies - mean platelet volume (MPV)• Studies for antibodies to FcεRI or IgE were not available in Israel for routine clinical work• Each patient, calculated the number of laboratory tests performed and the proportion of abnormal test results (J Allergy Clin Immunol 2012;129:1307-13)
  15. 15. RESULTS
  16. 16. Study group Control group Diagnoses of Control CU =12,778 pt =10,714 pt. Women = men = 4,306 women = men = 1,526 8,472 (66.3%) (33.6%) 9,188 (85.7%) (14.3%) Average age 45.3 +/- 18.5 years Average age 44.2 +/- 14.2 years(J Allergy Clin Immunol 2012;129:1307-13)
  17. 17. Thyroid disease and CU
  18. 18. (J Allergy Clin Immunol 2012;129:1307-13)
  19. 19. With in 10 yr(J Allergy Clin Immunol 2012;129:1307-13)
  20. 20. Other autoimmune disease and CU
  21. 21. (J Allergy Clin Immunol 2012;129:1307-13)
  22. 22. With in 10 yr(J Allergy Clin Immunol 2012;129:1307-13)
  23. 23. • few autoimmune diseases were diagnosed during the first 6 monthsafter the diagnosis of CU• most continuously revealed over more than 10 years• suggest that accompanying autoimmune diseases were independentlydiagnosed and not as part of the CU workup
  24. 24. • OR of pt with CU with additional autoimmune disease = 17.343 compared with control (95% CI, 14.222-21.148; P < .0005)• 1,872 pt with CU with autoimmune diseases - 12.5% (n =1591)  1 autoimmune disease - 2.1% (n = 263)  2 autoimmune diseases (hypothyroidism and another, mostly RA) - 0.1% (n= 16)  3 autoimmune diseases - 1 pt. 4 autoimmune diseases - 1 pt. 5 autoimmune diseases (J Allergy Clin Immunol 2012;129:1307-13)
  25. 25. Serologic and Labortory markers and CU
  26. 26. Abnormal high306 CU pt.with hypothyroidism have Antithyroid Ab( ATG,ATPO) (J Allergy Clin Immunol 2012;129:1307-13)
  27. 27. • Pt. CU group 11,514 pt. with euthyroid Lab CU patient Control OR P value With euthyroid ATPO Ab 312 6 24.24 < 0.0001 ATG 74 1 17.37 <0.0001 (J Allergy Clin Immunol 2012;129:1307-13)
  28. 28. Discussion• This study is the first large control study demonstrating a correlation between CU and the main autoimmune diseases and serologic markers• women affected twice as often as men
  29. 29. • Thyroid disease were most common autoimmune disease accopanying pt with CU from this study Pt with CU Dx - hypothyroidism = 10% - hypertrhyroidism = 2.6% signinicant than control and normal population group• Antithyroid peroxidase and antithyroglobulin more significant prevalent in Pt. with CU than control group and physician were also diagnosed thyroid disease
  30. 30. • Aversano et al hypothesized that inflamatory status induced by thyroid- stimulating hormone led to flares of urticaria and production of antithyroid antibodies• The author suggest that the association between CU and thyroid disease might due to share susceptability to autoimmune or chronic inflammatory process ( finding of other autoimmune disease were more common in CU pt.)
  31. 31. • Rheumatoid arthrits second most common autoimmune disease in pt. with CU - 1.9% of female pt. with CU (significant more prevalent than control group and normal population) - Rheumatoid factor +ve often in female and male pt. with CU than control• Type I DM, Sjögren syndrome, celiac disease and SLEsignificant more prevalent in female pt. with CU thancontrol
  32. 32. • Strengths of this study - large population of pt. with CU - compared with large match control group - retrospective study : correlation of CU and autoimmunity and proinflammatory marker• Limitation of study - retrospective study : to evaluate autoimmune diasease and serologic marker that have effect or relation to CU required detail information and closed follow up
  33. 33. Conclusion• Clinical implications: - CU is probably one of the autoimmune diseases - Understanding the disease process might help the development of individualized therapies and increase awareness of comorbidities, as well as help in the prediction of disease prognosis
  34. 34. • Over the past 2 decades, studies have suggested an autoimmune mechanism underlying the pathophysiology of CIU in up to 50% of the patients• Clinicians have also observed an association between CIU and thyroid antibodies in approximately 15 to 25% of CIU patients• purpose of study - to determine correlation of biomarkers for autoimmunity (ANA or ATA, either individually or in combination with the CU Index) and disease severity in CIU• CU index : commercial basophil histamine release assays to screen for a functional autoantibody to FcεRI Ann Allergy Asthma Immunol 108 (2012) 337–341
  35. 35. Methods• Retrospective analysis patients with an ICD-9 diagnosis of chronic idiopathic urticaria from October 1, 2007 through September 30, 2009 in allergy clinic at tertiary care in Wisconsin• 195 pt. (age ≥ 18) were included• Exclusion : if they had primarily physical or cholinergic urticaria, acute urticaria, food or drug-related urticaria, vasculitis, mastocytosis, or exclusively angioedema without evidence of urticaria. Ann Allergy Asthma Immunol 108 (2012) 337–341
  36. 36. • Classified into 2 groups: they - Controlled if they required only H1/H2 antihistamines with or without a leukotriene receptor antagonist (LTRA) for control of their hives - Refractory if they continued to have physical evidence of urticaria on this regimen Ann Allergy Asthma Immunol 108 (2012) 337–341
  37. 37. • Laboratory data - ANA - anti-thyroperoxidase antibody (ATPO) - anti-thyroglobulin antibody (ATG) - CU Index (basophil histamine release assay)• positive result were - CU Index (>10) - ANA (titer > 1:160) Ann Allergy Asthma Immunol 108 (2012) 337–341
  38. 38. Results• Demographic data• All four biomarkers (CU Index, ANA, ATG, ATPO) were measured in 25% ofCIU patients• at least 1 biomarker was measured in 84% of patients• No autoimmune biomarker was measured in 32 (16%) CIU patients Ann Allergy Asthma Immunol 108 (2012) 337–341
  39. 39. Results• Percentage of patients with positive autoimmune biomarkers Ann Allergy Asthma Immunol 108 (2012) 337–341
  40. 40. Results• Autoimmune biomarkers and disease severity 80% 46% 50% 30% Ann Allergy Asthma Immunol 108 (2012) 337–341
  41. 41. Results• Test characteristics of combinations of autoimmune biomarkers 4.5 2.3 3.1 Ann Allergy Asthma Immunol 108 (2012) 337–341
  42. 42. Results Sensitivity, specity,PPV,NPV for identify a refractory outcome in CIU • CU Index has superior SPEC and PPV for identifying a refractory outcome in CIU • combinations of ANA and anti-thyroid antibodies slightly better SENS and NPV Ann Allergy Asthma Immunol 108 (2012) 337–341
  43. 43. • Cost of order the autoimmune biomarkers - ANA= $84.20 - ATG = $128.00 - ATPO= $118.00 - CU Index = $436.00 - combination of the ANA, ATG, and ATPO = $330.20• Need for establishing screening tools to identify pt. who are likely to remain refractory to conventional therapy and allow for an optimal and appropriate management in a timely and cost-effective manner Ann Allergy Asthma Immunol 108 (2012) 337–341
  44. 44. Mediator of hives and swellingMast cell (cutaneous) Histamine Prostaglandin D Leukotrienes C and D Platelet activating factor or 1-O-alkyl-2- acetyl-sn-glyceryl-3-phosphorylcholineComplement system Anaphylatoxins C3a, C4a,C5a: histamineHageman factor dependent bradykininpathwayMononuclear cells Histamine-releasing factors, chemokine

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