2/17/2014 Conflict of Interests Chronic Urticaria: Updates on Diagnostic Testing • Author of urticaria practice parameters and Therapy from the Practice Parameter • Principal Investigator Novartis and Genentech • IIS Novartis/Genentech Jonathan A. Bernstein, M.D. • AAAAI BOD Professor of Medicine University of Cincinnati • Editor in Chief Journal of Asthma Department of Internal Medicine Division of Immunology/Allergy Section At the end of this lecture the participant will be able to: The Diagnosis and Management of Acute and Chronic Urticaria: 2014 Update 1) Discuss the diagnostic approach to acute and chronic Chief Editors urticaria Jonathan A. Bernstein, MD, David M. Lang, 2) Explain the dos and don’ts of evaluating patients with MD, David A. Khan, MD chronic urticaria Workgroup Contributors 3) Determine the best treatment approach for patients with chronic urticaria Timothy Craig, DO; David Dreyfus, MD; Fred Hsieh, MD; Javed Sheikh, MD; David Weldon, MD; and Bruce Zuraw, MD History of the Updated Urticaria Parameter Areas of Controversy • Began as Urticaria and Angioedema early 2008 • Diagnostic testing • – Laboratory testing Divided into Angioedema and Urticaria parameters – ASST/APST • Angioedema parameter accepted JACI March 14, 2013 – d-dimers • Urticaria guideline accepted JACI February 12, 2014 – Skin testing – 198 pages; 54,053 words • Treatments – Euthyroid patients with autoantibodies – 11 tables and 4 figures; annotations with flow diagrams for – Autoantibody associated urticaria (aka autoimmune urticaria) acute and chronic urticaria – Autoimmune disease – 658 graded references – Helicobacter pylori, Celiac disease – Grade process used for analysis of cyclosporine – Low histamine diets – Highly vetted by the JTF, AAAAI, ACAAI, external reviewers – High dose H1-antihistamines nationally and internationally – Step care treatment approach – Role of Omalizumab (trials would have been omitted if guideline was published earlier) 1 2/17/2014 Case Presentation • SG is a 26 y/o female with new onset hives with lip swelling for 5 days Question #1 • Past history of mild asthma, allergic rhinitis with oral allergy syndrome to melons What diagnostic testing would you order for this and avocado, gastroesophageal reflux disease and psoriasis patient at the time of her initial visit? • Also with gluten intolerance (negative celiac work-up) • Denies relationship of hives to foods or prescription/OTC medications. A. CBC with differential and WSR – Took ibuprofen the last two nights for headache – Also was taking an over the counter pure saffron extract supplement for weight loss which she stopped two days prior to her visit B. ANA, RF • No history of thyroid disease, chronic infections, autoimmune disorders or malignancies; hives not associated with any physical stimuli C. TSH and thyroid antibodies • The hives are evanescent, very pruritic affecting 45% of her body D. All of the above • Family history significant for father and identical twin sister with history of urticaria • Primary care prescribed a methylprednisolone dose pack and diphenhydramine E. None of the above 25mg as needed with some benefit but still with hives at the time of the visit; feels nervous from the corticosteroids SUMMARY STATEMENT 6: Most often acute Table 1. Causes of acute urticaria and/or angioedema urticaria is a self-limiting condition that will resolve spontaneously in less than six weeks. • Food allergies (IgE mediated) Extensive evaluation for causes not suggested by • Adverse reactions to allergen immunotherapy • Adverse medication reactions (e.g. opiates, ACE inhibitors, the history or physical examination is not cost • NSAIDS) effective and has not been associated with • Contact urticaria (e.g., plant, animal) improved outcomes.(C) • Early contact dermatitis (e.g., poison ivy, nickel) • Exacerbation of physical urticaria (e.g., dermographism, • cholinergic urticaria) SUMMARY STATEMENT 7: Common causes of • Papular urticaria due to insect sting / bite (e.g., scabies, acute urticaria and angioedema, including • fleas, bed bugs) medications and foods, should be identified by a • Infection (e.g., Parvo virus B19, Epstein-Barr virus) detailed history and eliminated if possible. (C) • Food or envenomation/ ingested toxin (e. g. scombroid) Question #2 What should the initial treatment be for this patient? SUMMARY STATEMENT 8: In most cases, A. A non-sedating second generation H1-antagonist antihistamines are efficacious for therapy of acute once a day urticaria and angioedema. (B) B. A non-sedating second generation H1-antagonist in the AM and first generation sedating antihistamine at bedtime SUMMARY STATEMENT 9: In severe cases, oral C. Double the dose of non-sedating second generation corticosteroids may be necessary to treat acute antihistamine with as needed first generation urticaria and angioedema. In patients with poor antihistamine at bedtime response to antihistamines, a brief course of oral D. A non-sedating second generation H1-antagonist in corticosteroids may also be required while the AM + an H2 antagonist twice a day attempting to eliminate suspected triggers and develop an effective treatment plan. (C) E. All of the above 2 2/17/2014 Figure 1. Step-approach treatment for chronic urticaria and angioedema STEP 4 Follow Up Visit – 2 weeks later Add an alternative agent •Omalizumab or cyclosporine •Other anti-inflammatory • Still with daily hives covering 35-45% of body and very agents,immunosuppressants, or biologics pruritic STEP 3 Dose advancement of potent antihistamine (e.g. hydroxyzine or doxepin) as tolerated • Using diphenhydramine 25mg as needed 2-3 times a STEP 2 One or more of the following: day as the daily second generation antihistamine by •Dose advancement of 2nd generation antihistamine used in Step 1 •Add another second generation antihistamine itself is ineffective •Add H2- antagonist •Add leukotriene receptor antagonist – Experiencing fatigue •Add 1st generation antihistamine to be taken at bedtime STEP 1 • Concerned the hives may be due to food but not sure •Monotherapy with second generation antihistamine •Avoidance of triggers (e.g., NSAIDs) and relevant physical factors if which one physical urticaria/angioedema syndrome is present. • Also wandering if she has an autoimmune disorder •Begin treatment at step appropriate for patient’s level of severity and previous treatment history causing the hives as there is a family history •At each level of the step-approach, medication(s) should be assessed for patient tolerance and efficacy – No symptoms of other rashes, arthritis, weight loss, •“Step-down” in treatment is appropriate at any step, once consistent control of urticaria/angioedema is achieved stomatitis, fevers… SUMMARY STATEMENT 13: Evaluation of a patient with CU should involve Laboratory Evaluation consideration of various possible causes. Most cases do not have an Routine evaluation. Testing should be selective. There is an honest identifiable cause [C] difference of opinion concerning the appropriate tests that should routinely be performed for patients with CU in the absence of etiologic SUMMARY STATEMENT 26: The initial patient evaluation should be focused to determine (via history and physical exam) whether the lesions that patients considerations raised by a detailed history and careful physical exam. describe are consistent with CU. [D] A majority of members of the Practice Parameters Task Force expressed a consensus for the following routine tests in managing a SUMMARY STATEMENT 27: The medical work-up of a patient with CU should patient with CU without atypical features: be done keeping in mind that CU is of undetermined etiology in the majority of cases. [C] Complete blood count with differential Erythrocyte sedimentation rate and/or C-reactive protein SUMMARY STATEMENT 28: After a thorough history and physical examination, Liver enzymes no diagnostic testing may be appropriate for patients with CU; however, Thyroid stimulating hormone 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 The utility of performing the above tests routinely for CU patients has not been hypersensitivity skin testing for inhalants or foods, is not warranted. Routine established. laboratory testing in patients with CU, whose history and physical examination lack atypical features, rarely yields clinically significant findings.[C] Additional evaluation may be warranted based upon patient circumstances, and may include Summary Statement #28 (cont) but not be limited to the diagnostic tests listed below. A thorough history and meticulous physical exam is essential for determining whether these additional tests are appropriate: Skin biopsy Limited testing may be justified based on its Physical challenge tests Complement system: e.g. C3, C4, and CH50 “reassurance value”; however, extensive routine Stool analysis for ova and parasites Urinalysis testing is not favorable from a cost-benefit Hepatitis B and C serologies Chest radiograph and/or other imaging studies standpoint, and does not lead to improved Antinuclear antibody (ANA) Rheumatoid factor, anti-citrullinated protein patient care outcomes. Cryoglobulin levels Serologic and/or skin testing for immediate hypersensitivity Thyroid autoantibodies Serum protein electrophoresis More detailed laboratory testing and/or skin biopsy merits consideration if urticaria is not responding to therapy as anticipated.