Presentation on theme: "Updates from the New Urticaria Practice Parameter"— Presentation transcript:
1Updates from the New Urticaria Practice Parameter David A. Khan, MDProfessor of MedicineAllergy & Immunology Program DirectorDivision of Allergy & ImmunologyUniversity of Texas Southwestern Medical Center - Dallas
2Disclosures Research Grants Speaker Honoraria Organizations: NIH, Vanberg Family FundSpeaker HonorariaMerck, Genentech, Viropharma, BaxterOrganizations:Joint Task Force on Practice ParametersAll medications other than antihistamines are considered “off-label” for treatment of chronic urticaria
3ObjectivesTo be able to discuss limitations and recommendations on testing in chronic urticariaTo develop a step-wised approach to chronic urticariaTo gain an understanding of the use of alternative agents in refractory chronic urticaria
4The Diagnosis and Management of Acute and Chronic Urticaria: 2014 Update Chief Editors Jonathan Bernstein, MD; David Lang, MD; David Khan, MD Workgroup Contributors Timothy Craig, DO; David Dreyfus, MD; Fred Hsieh, MD; Javed Sheikh, 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
5Urticaria Parameter Update Manuscript in submissionSummary statements and other recommendations presented may changePublication in 2014?
6Urticaria Practice Parameter SectionsExecutive SummaryAcute UrticariaDiagnosis and Management of Chronic UrticariaPhysical Urticaria/AngioedemaDifferential DiagnosisTreatment for Acute and Chronic Urticaria
7Diagnostic Evaluation in Urticaria How Many and What Tests Are Required?
8Most CU is IdiopathicSUMMARY STATEMENT 13: Evaluation of a patient with CU should involve consideration of various possible causes. Most cases do not have an identifiable cause [C]
9Chronic Urticaria Etiologies IdiopathicPhysicalAutoantibody AssociatedUrticarial VasculitisSystemic diseases (other than perhaps thyroid disease) are very rarely associated with CU
10Tests For Physical Urticaria ColdIce cube testLocalized HeatTest tube water 44ºCCholinergicExercise for min.Leg immersion in 44ºC bathDelayed PressureSand bag test: 15 lb weight for 15 minutesDermographismStroking skinSolarSpecific wavelength light exposureAquagenicWater compressVibratoryVortex for 5 minutes
11Tests for Autoantibodies in CU Skin testsAutologous serum skin testAutologous plasma skin testCommercially Available TestsCU Index (IBT Labs)Measures histamine release from donor basophils activated by patient seraIGERAB (National Jewish Labs)Measures CD203c by flow cytometry on donor basophils activated by patient sera
12Autoantibodies in CUSUMMARY 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)
13Autoantibody TestingSUMMARY 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)
14Autoimmune 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
15Routine 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)
16Role 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.
17Urticarial Vasculitis 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)
18Cutaneous Features of UV Urticaria descriptionPainful, tender, burning or pruriticDuration of lesions24-72 hrs (may be only present in ~40%)Lesions may resolve with purpura or hyperpigmentationTosoni C. et al. Clin Exp Derm 2008;34:
19Laboratories in UV All forms of UV ESR50% ANA +dsDNA –HUV/HUVS (hypocomplomentemic UV/ syndrome) C3 ,C4, CH50 C1qAnti C1q antibodies present in 100% of HUVAlso seen in Felty’s syndrome, SLE, Sjogren’s syndrome, and MPGNKallenberg CG. Autoimmun Rev 2008;7:612-5.
20Thyroid LabsSUMMARY 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]
21Skin BiopsySUMMARY 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]
22Skin TestingSUMMARY 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]
23Diagnostic Labs in CUSystematic review of 29 studies involving 6462 urticaria patientsLarge 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 responsibleMajority were cutaneous vasculitisKozel MM, et al.. J Am Acad Dermatol 2003; 48 (3):
24Diagnostic Labs in CU Most authors concluded that history is important Most authors concluded that routine laboratory tests are not requiredLaboratories should be guided by the history, which is the most important instrument in finding an etiologyKozel MM, et al. J Am Acad Dermatol 2003; 48 (3):
25356 CU pts seen at Cleveland Clinic Retrospective study to investigate the proportion of abnormal test results in patients with CU leading to a change in management and in outcomes of care356 CU pts seen at Cleveland ClinicTarbox JA et al. Ann Allergy Asthma Immunol 2011;107:239 –243.
2617% of 1,872 ordered tests were abnormal Tarbox JA et al. Ann Allergy Asthma Immunol 2011;107:239 –243.
271/356 (0.28%) benefitted from testing! 1 patient with hypothyroidism with normal TSH and elevated microsomal AB responded to higher dose thyroxineTarbox JA et al. Ann Allergy Asthma Immunol 2011;107:239 –243.
28Diagnostic 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.
29Routine LabsSummary 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]
38Principles of Step Therapy Begin treatment at step appropriate for patient’s level of severity and previous treatment historyAt 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
40H1 Antihistamines in CUSUMMARY 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)
42Higher 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)
43High Dose Antihistamines in CU Cetirizine: conflicting studiesFexofenadine: no difference between 60 mg, 120 mg and 240 mg twice a dayDesloratadine20 mg > 5 mg in cold urticariaLevocetirizine and desloratadineHigher doses better
44High Dose Antihistamines in CU Staevska M et al. J Allergy Clin Immunol 2010;125:
45H2 AntihistaminesSUMMARY 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)
46Leukotriene 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.
481st 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)
49Hydroxyzine 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)
50CorticosteroidsSUMMARY 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)
52Refractory Chronic Urticaria SUMMARY STATEMENT 84: CU patients who are not adequately controlled on maximally tolerated antihistamine therapy (e.g., doxepin at a dose of mg/day) may be considered to have refractory CU. (E)
53Alternative AgentsSUMMARY STATEMENT 85: A number of alternative therapies have been studied for the treatment of CU; these therapies merit consideration for patients with refractory CU. (D)
54Rationale for Alternative Agents in Chronic Urticaria While most urticaria is antihistamine responsive, not all patients have adequate control with antihistamine therapy at any doseGlucocorticoids while typically effective, have predictable and nearly universal toxicity for treatment of chronic urticariaAlternative AgentsImmunomodulatoryImmunosuppressantOther
55Evidence for Alternative Therapies in CU Overall the evidence for most alternative therapies is weakFew agents have well designed randomized placebo-controlled studiesMost studies have small number of participants
58Anti-inflammatory Agents SUMMARY STATEMENT 86: Anti-inflammatory agents including dapsone, sulfasalazine, hydroxychloroquine, and colchicine have limited evidence for efficacy in CU and some require laboratory monitoring for adverse effects.(C) These agents are generally well tolerated, may be efficacious in properly selected patients, and may be considered for treatment of antihistamine refractory CU patients.(D)
59ImmunosuppressantsSUMMARY STATEMENT 87: Several immunosuppressant agents have been used in patients with refractory CU. Cyclosporine has been studied in several randomized controlled trials. (A) For this reason, cyclosporine was selected for closer examination as to the quality of evidence supporting its administration in patients with refractory chronic urticaria/angioedema.
60Khan DA. In: Maibach HI, Gorouhi F ed Khan DA. In: Maibach HI, Gorouhi F ed. Evidence Based Dermatology 2nd ed. 2011
61Trojan T, Khan DA. Curr Opin Allergy Immunol 2012;12:412-20.
62Trojan T, Khan DA. Curr Opin Allergy Immunol 2012;12:412-20.
63OmalizumabSUMMARY STATEMENT 88: In contrast to other alternative agents for refractory CU, the therapeutic utility of omalizumab has been supported by findings from large double-blind randomized controlled trials and is associated with a relatively low rate of clinically significant adverse effects. On the basis of this evidence, omalizumab should be considered for refractory CU if from an individualized standpoint a therapeutic trial of omalizumab is favorable from the standpoint of balancing the potential for benefit with the potential for harm/burden, and the decision to proceed is consistent with patient values and preferences. (A)
67Omalizumab in CU refractory to H1 plus H2 and/or LTRA therapies
68Selecting an Alternative Agent SUMMARY STATEMENT 93: Multiple factors are involved in selecting an alternative agent in refractory CU patients including but not limited to the presence of comorbid factors, frequency of treatment-related visits, cost, rapidity of response, adverse effects and patient values and preferences. The potential for harm and burden association with a given alternative agent is extremely important and needs to be weighed against the patient’s potential for benefit, current quality of life, and any adverse effects from current therapy for their CU. (D)
69Personal Preferences in Alternative Therapies I typically start with dapsoneHydroxychloroquine, sulfasalazine other similar alternativesIn patients demonstrating steroid toxicity, I start with tacrolimusbetter tolerated than cyclosporine in my experienceOmalizumab or mycophenolate used after these agents
70How Long to Treat? Once successful alternative agent found Taper off steroidsTaper off other medicationsI treat with alternative agent until urticaria free for at least 3 months then taper over ~3 monthsSome patients require long term (years) usageFind lowest dose to control CU
71Why Aren’t Alternative Agents Used More? FearLack of TrainingOutside of comfort zone
73ConclusionsIn the absence of history, diagnostic tests have a low yield in evaluation of CUThe presence of autoantibodies may not aid in management of CU patientsUpcoming urticaria guidelines will provide a very comprehensive resource to aid in management of urticaria patientsStep-wised approach to chronic urticaria should aid allergists in managing patients