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Updates from the New Urticaria Practice Parameter David A. Khan, MD Professor of Medicine Allergy & Immunology Program Director Division of Allergy & Immunology University of Texas Southwestern Medical Center - Dallas
Disclosures • Research Grants • NIH, Vanberg Family Fund • Speaker Honoraria • Merck, Genentech, Viropharma, Baxter • Organizations: • Joint Task Force on Practice Parameters All medications other than antihistamines are considered “off-label” for treatment of chronic urticaria
Objectives To be able to discuss limitations and recommendations on testing in chronic urticaria To develop a step-wised approach to chronic urticaria To gain an understanding of the use of alternative agents in refractory chronic urticaria
The Diagnosis and Management of Acute and Chronic Urticaria: 2014 UpdateChief EditorsJonathan Bernstein, MD; David Lang, MD; David Khan, MDWorkgroup Contributors Timothy Craig, DO; David Dreyfus, MD; Fred Hsieh, MD;JavedSheikh, MD; David Weldon, MD; and Bruce Zuraw, MD Task Force Reviewers David I. Bernstein, MD; Joann Blessing-Moore, MD; Linda Cox, MD; Richard A. Nicklas, MD; John Oppenheimer, MD; Jay M. Portnoy, MD; Christopher R. Randolph, MD; Diane E. Schuller, MD; Sheldon L. Spector, MD; Stephen A. Tilles, MD; and Dana Wallace, MD
Urticaria Parameter Update • Manuscript in submission • Summary statements and other recommendations presented may change • Publication in 2014?
Urticaria Practice Parameter • Sections • Executive Summary • Acute Urticaria • Diagnosis and Management of Chronic Urticaria • Physical Urticaria/Angioedema • Differential Diagnosis • Treatment for Acute and Chronic Urticaria
Diagnostic Evaluation in Urticaria How Many and What Tests Are Required?
Most CU is Idiopathic SUMMARY STATEMENT 13: Evaluation of a patient with CU should involve consideration of various possible causes. Most cases do not have an identifiable cause [C]
Chronic Urticaria Etiologies Systemic diseases (other than perhaps thyroid disease) are very rarely associated with CU Idiopathic Physical Autoantibody Associated Urticarial Vasculitis
Tests for Autoantibodies in CU • Skin tests • Autologous serum skin test • Autologous plasma skin test • Commercially Available Tests • CU Index (IBT Labs) • Measures histamine release from donor basophils activated by patient sera • IGERAB (National Jewish Labs) • Measures CD203c by flow cytometry on donor basophils activated by patient sera
Autoantibodies in CU SUMMARY STATEMENT 22: The utility of the autologous serum skin test (ASST) and the autologous plasma skin test (APST) is unclear, as evidence has not clearly demonstrated this testing identifies a distinct subgroup of patients with CU. Current evidence does not support routine performance of ASST or APST in patients with CU. (C)
Autoantibody Testing SUMMARY STATEMENT 30: While commercial assays are now available, the utility of testing for auto-antibodies to the high-affinity IgE receptor or autoantibodies to IgE has not been determined.(C)
Autoimmune Tests Usually Not Warranted SUMMARY STATEMENT 15: Serology to diagnose underlying autoimmune diseases (e.g., connective tissue disease) is not warranted in the initial evaluation of CU. (B) No need to get ANA routinely in patients with CU
Routine Testing for H Pylori and Celiac Not Required SUMMARY STATEMENT 19: The co-occurrence of CU with a number of conditions, including Helicobacter pylori infection and celiac disease, has been reported. However, evidence does not support testing for these conditions in a CU patient with an otherwise unremarkable history and physical examination. Moreover, there are no convincing data which demonstrate that treatment based on abnormal test results consistent with these conditions being present leads to improvement or change in the course of CU. (C)
Role of H. pylori in CU ? Conclusion: The evidence that H. pylori eradication leads to improvement of chronic urticaria outcomes is weak and conflicting; this leads to a weak recommendation for routine H. pylori eradication for patients with chronic urticaria. Shakouri A. et al. Curr Opin Allergy Immunol 2010;10:362-9.
UrticarialVasculitis May Look Like CIU SUMMARY STATEMENT 18: Urticarial vasculitic lesions may sometimes be evanescent lasting less than 24 hours, similar to CU; for this reason, urticarial vasculitis cannot be completely excluded based on the history of lesions spanning less than 24 hours. (B)
Cutaneous Features of UV • Urticaria description • Painful, tender, burning or pruritic • Duration of lesions • 24-72 hrs (may be only present in ~40%) • Lesions may resolve with purpura or hyperpigmentation Tosoni C. et al. Clin Exp Derm 2008;34:166-70.
Laboratories in UV • All forms of UV • ESR • 50% ANA + • dsDNA – • HUV/HUVS (hypocomplomentemic UV/ syndrome) • C3 ,C4, CH50 • C1q • Anti C1q antibodies present in 100% of HUV • Also seen in Felty’s syndrome, SLE, Sjogren’s syndrome, and MPGN • Kallenberg CG. Autoimmun Rev 2008;7:612-5.
Thyroid Labs SUMMARY STATEMENT 29: Screening for thyroid disease is of low yield in patients without specific thyroid-related symptoms or history of thyroid disease. Elevated levels of anti-thyroglobulin or anti-thyroid antibodies in euthyroid (i.e. normal TSH) individuals are commonly detected, although the clinical implications of this finding are unclear. [C]
Skin Biopsy SUMMARY STATEMENT 32: Skin biopsy may be performed when vasculitis is suspected, such as in refractory CU, or when other non-urticarial immunological skin diseases are a consideration. Routine skin biopsies are not required in most cases of CU. [D]
Skin Testing SUMMARY STATEMENT 33: Immediate hypersensitivity skin or serologic testing for food or other allergens is rarely useful, and is not recommended on a routine basis. [D]
Diagnostic Labs in CU • Systematic review of 29 studies involving 6462 urticaria patients • Large variability in determining an etiology: 1-84% (median 38%) • Most studies excluding physical urticarias had lowest identifiable diagnoses (1-20%) • Only 1.6% patients thought to have an internal disease responsible • Majority were cutaneous vasculitis Kozel MM, et al.. J Am Acad Dermatol 2003; 48 (3): 409-16
Diagnostic Labs in CU • Most authors concluded that history is important • Most authors concluded that routine laboratory tests are not required • Laboratories should be guided by the history, which is the most important instrument in finding an etiology Kozel MM, et al. J Am Acad Dermatol 2003; 48 (3): 409-16
Retrospective study to investigate the proportion of abnormal test results in patients with CU leading to a change in management and in outcomes of care 356 CU pts seen at Cleveland Clinic Tarbox JA et al. Ann Allergy Asthma Immunol2011;107:239 –243.
17% of 1,872 ordered tests were abnormal Tarbox JA et al. Ann Allergy Asthma Immunol2011;107:239 –243.
1/356 (0.28%) benefitted from testing! 1 patient with hypothyroidism with normal TSH and elevated microsomal AB responded to higher dose thyroxine Tarbox JA et al. Ann Allergy Asthma Immunol2011;107:239 –243.
Diagnostic Testing in CU SUMMARY STATEMENT 28: After a thorough history and physical examination, no diagnostic testing may be appropriate for patients with CU; however, limited routine lab testing may be performed to exclude underlying causes. Targeted lab testing based on clinical suspicion is appropriate. Extensive routine testing for exogenous and rare causes of CU, or immediate hypersensitivity skin testing for inhalants or foods, is not warranted.
Routine Labs Summary Statement 28 (cont’d): Routine laboratory testing in patients with CU, whose history and physical examination lack atypical features, rarely yields clinically significant findings.[C]
Drug Exanthem vs. Urticaria Drug Exanthem Urticaria
angioedema urticaria Multiforme-looking lupus (Rowell syndrome) subacute cutaneous lupus urticaria pigmentosa Sweet syndrome Urticarial phase of bullouspemphigoid fixed drug eruption Brodell LA, Beck LA. Ann Allergy Asthma Immunol 2008;100:181-8.
Principles of Step Therapy Begin treatment at step appropriate for patient’s level of severity and previous treatment history At each level of the step-approach, medication(s) should be assessed for patient tolerance and efficacy or discontinuation to avoid unnecessary polypharmacy. NOTE: “Step-down” in treatment is appropriate at any step described, once consistent control of urticaria/angioedema is achieved
H1 Antihistamines in CU SUMMARY STATEMENT 76: H1 antagonists are effective in the majority of patients with CU but may not achieve complete control in all patients. (C) SUMMARY STATEMENT 77: Second-generation antihistamines are safe and effective therapies in CU and are considered first-line agents. (A)
Higher Dose H1 Antihistamines SUMMARY STATEMENT 78: Higher doses of second-generation antihistamines may provide more efficacy but data are limited and conflicting for certain agents. (B)
High Dose Antihistamines in CU • Cetirizine: conflicting studies • Fexofenadine: no difference between 60 mg, 120 mg and 240 mg twice a day • Desloratadine • 20 mg > 5 mg in cold urticaria • Levocetirizine and desloratadine • Higher doses better
High Dose Antihistamines in CU Staevska M et al. J Allergy Clin Immunol 2010;125:676-82.
H2 Antihistamines SUMMARY STATEMENT 80: H-2 antihistamines, taken in combination with first and second-generation H-1 antihistamines, have been reported to be more efficacious compared to H-1 antihistamines alone for the treatment of CU. (A) However, this added efficacy may be related to pharmacologic interactions and increased blood levels of first-generation antihistamines. (B) As these agents are well tolerated, the addition of H2-antagonists may be considered when CU is not optimally controlled with second-generation antihistamine monotherapy.(D)
Leukotriene receptor antagonists SUMMARY STATEMENT 81: Leukotriene receptor antagonists have been shown in several but not all randomized controlled studies to be efficacious in patients with CU.(A) Leukotriene receptor antagonists are generally well tolerated (A). Leukotriene receptor antagonists may be considered for CU patients with unsatisfactory responses to 2nd generation antihistamine monotherapy.
1st Generation Antihistamines SUMMARY STATEMENT 79: First-generation antihistamines have proven efficacy in the treatment of CU. Efficacy of first-generation antihistamines is similar to second-generation antihistamines but sedation and impairment are greater with first-generation antihistamines, especially with short-term use. (A) First-generation antihistamines may be considered in patients who do not achieve control of their condition with higher dose second-generation antihistamines.(D)
Hydroxyzine and Doxepin SUMMARY STATEMENT 82: Treatment with hydroxyzine or doxepin may be considered in patients who remain poorly controlled with dose advancement of second-generation antihistamines, and the addition of H2-antihistamines, first-generation H-1 antihistamine at bedtime, and/or anti-leukotrienes.(D)
Corticosteroids SUMMARY STATEMENT 83: Systemic corticosteroids are frequently used for refractory CU patients, but no controlled studies have demonstrated efficacy. In some patients, short-term use (e.g. 1-3 weeks duration) may be required to gain control of their disease until other therapies can achieve control. Because of the risk of adverse effects with systemic corticosteroids, long-term use for treatment of CU patients should be avoided as much as possible. (D)