They re Scratching and You re Scratching Your Head: An Approach to the Diagnosis and Management of Acute and Chronic Urticaria
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1 They re Scratching and You re Scratching Your Head: An Approach to the Diagnosis and Management of Acute and Chronic Urticaria Adelle R. Atkinson, MD, FRCPC Sea Courses May/June 2017
2 Copyright 2017 by Sea Courses Inc. All rights reserved. No part of this document may be reproduced, copied, stored, or transmitted in any form or by any means graphic, electronic, or mechanical, including photocopying, recording, or information storage and retrieval systems without prior written permission of Sea Courses Inc. except where permitted by law. Sea Courses is not responsible for any speaker or participant s statements, materials, acts or omissions.
3 Learning Objectives At the end of this session, you will be able to: 1. Discuss the differential diagnoses of both acute and chronic urticaria 2. Describe the work-up and management of various forms of acute and chronic urticaria 3. describe an approach to the physical urticarias and their management
4 Acute and Chronic Urticaria
5 Definition Acute Urticaria The presence of hives every day or almost every day with a duration of less than 6 weeks Mast cell and basophil activation Chronic Urticaria The presence of hives every day or almost every day with a duration > 6 weeks But.Chronic Urticaria has to start somewhere, so patients need periodic re-evaluation
6 Allergy - Diagnosis History specifics around the urticaria and whether there might have been a trigger (food, drug, environmental)? Associated angioedema action taken (antihistamines, epi-pen, 911) time to resolution of symptoms presence of a viral illness exercise, heat, cold or other physical triggers
7 Allergy - Diagnosis History continued Full review of systems for any other signs or symptoms of chronic disease thyroid disease, malignancy, autoimmunity, chronic viral infection etc. previous ingestions of the food/drug in question previous trials of therapy Personal and family history of atopy
8 Allergy - Diagnosis Physical Examination presence of existing allergic manifestations - angioedema, hives swollen nasal mucosa signs and symptoms of atopy Evidence of manifestations of any chronic disease
9 Physical Examination CU lesions typically edematous pink or red wheals of variable size and shape with surrounding erythema and are usually pruritic Usually NOT painful or burning (more c/w vasculitis) Individual wheals usually fade within 24 to 48 hours with others forming
10 Skin Prick Testing
11 Skin Prick Testing Histamine Saline Peanut
12 Allergy - Diagnosis SPT must be tailored to each individual patient, one must not do a panel of screening tests looking for a positive reaction SPT is highly reproducible, and can be used for food, penicillin and environmental allergies the negative predictive value of SPT is very high in the order of 98 to 99% the PPV of SPT is variable -- unknown for penicillin and environmental, less than 50% for some foods
13 Allergy - Diagnosis Intracutaneous Testing used in most centres only with penicillin, vaccines and venom not used with environmental and food used after a negative SPT by doing an intradermal injection no good evidence that it adds to the SPT, many false positives needs to be compared with the gold standard Autologous Serum Skin Test (ASST) Utility not clear, only considered for CU Currently not routinely performed
14 Intracutaneous testing
15 Allergy - Diagnosis Radioallergosorbent Test (RAST) in vitro test looking at specific IgE to specific allergens high negative predictive value positive predictive value low SPT more sensitive Offers some useful information and is particularly useful when SPT is not possible
16 Rast Testing
17 Rast Testing Anti-IgE Antigen IgE
18 Allergy - Diagnosis Double-Blind, Placebo- Controlled Food Challenge gold standard for the diagnosis of food allergy occasional false negatives must be done under supervision in a patient with a positive SPT and a questionable history a similar protocol has not been tried with penicillin
19 Acute Urticaria More likely to be associated with an identifiable condition Usually resolves spontaneously Needs a careful Hx and PE
20 Acute Urticaria Differential Diagnosis to consider after careful history and physical examination (and review of photos if available! especially if the patient is currently asymptomatic) Infections Viral, bacterial or parasitic IgE mediated reaction to: food, drugs Insect stings and bites Latex Blood products Direct mast cell activation Narcotics Muscle relaxants Vancomycin Radio contrast material Stinging nettle (urtica dioica) NSAIDS
21 Acute Urticaria Management Removal of offending agent First and second generation antihistamines Discussion with patients/families around the sedating side effects of first generation Brief course of oral steroids BUT there must be a plan as this is not a long term solution
22 Chronic Urticaria Less likely associated with an identifiable condition 0.5 to 5% of the general population May have both urticaria and angioedema occurring together or separately Histamine is the predominant mediator Activation of the coagulation cascade including increased prothrombin fragment F1 + 2 and D-dimer levels has been described and may be a marker of severity
23 Chronic Urticaria 30 50% of patients with CU produce specific IgG antibodies against the FcεR1αsubunit component of the high-affinity IgE receptor and 5 to 10% produce IgG antibodies against IgE itself Routine testing for food or inhalents, and extensive laboratory testing not recommended as it is not cost-effective and does not lead to improved patient outcomes Targeted laboratory testing based on Hx and PE is appropriate CBC and differential, ESR and/or CRP, liver enzymes, thyroid-stimulating hormone measurement This limited testing may be useful in patients with nothing in the history and physical to pick up rare cases (likely more in adults)
24 Chronic Urticaria Differential Diagnosis to consider after careful history and physical examination (and review of photos if available! especially if the patient is currently asymptomatic) Chronic idiopathic urticaria - majority Chronic viral infection ie: hepatitis B and C, EBV, HSV, Helicobacter pylori, helminthic parasitic infections Complement deficiencies Croyglobulinemia (eg. With Hepatitis C and CLL) Serum Sickness or other type III reactions Connective tissue diseases (SLE, JIA, thyroid disease) Endocrine disorders or hormonal therapies (eg. Ovarian tumors and OCP use) Mastocytosis/mastocytoma Urticarial vasculitis (hives usually last >24 hours) Malignancy
25 Chronic Urticaria But.. It is not recommended to do a workup for any of these disorders without evidence of additional features on history and physical examination tht suggest them Eg. Thyroid antibodies are frequently found in patients with CU and do not seem to be of clinical significance in the absence of associated clinical features Angioedema in the absence of urticaria goes down a different DDx pathway including: hereditary angioedema, ACE inhibitor associated angioedema etc.
26 Chronic Urticaria Management Avoid NSAIDs, heat, tight clothing No evidence to avoid any foods or other pseudoallergens
27 Stepwise Approach to the management of CIU 1. First-lie treatment is second-generation H1 antihistamines 2. Second-line therapy is up-dosing second-generation H1 antihistamins 3. Third-line treatment is omalizumab, recommended now before using Cyclosporin A 4. H2 antihistamines not included in the algorithm (case by case only) 5. Avoid first-generation H1 antihistamines based on benefitto-risk ratio 6. Corticosteroids considered only for short-term intervention; avoid as long-term treatment 7. Cyclosporin A for refractory CIU not responsive to other treatments
28 The Physical Urticarias
29 The Definition A subgroup of chronic urticaria (CU) Lesions reproducibly triggered by physical stimuli including: Cold Heat Physical pressure Vibration Water Sunlight exercise
30 The Definition Physical stimulation incites the characteristic wheal and flare Can also cause angioedema Skin manifestations usually localized to the areas exposed to the stimuli (some systemic cases) Can occur in isolation or with other chronic urticaria conditions Pathogenesis unknown
31 Abijian et. al. Curr Allergy Asthma Rep 2012
32 The Background 0.5% of the general population has a PU Up to 25% of patients with CU have a PU
33 The History Duration & Frequency Description of the lesions (photos) Pruritis?/associated angioedema Context when the lesions occurred Management and response? History of atopy? Related to: Cold Heat Physical pressure Vibration Water Sunlight exercise
34 Simple Dermatographism (Urticaria Factitia) Most common form of PU Usually affects young adults Mean duration 6.5 years Development of itchy wheals induced by mild stroking, rubbing or scratching Whealing occurs quickly and lasts 0.5 to 2 hours
35 Simple Dermatographism Provocation testing: (Urticaria Factitia) Rubbing the skin of the upper back or the volar of the forearm lightly with a smooth blunt object (dermographometer, tongue depressor) Assess skin after 10 minutes Threshold testing
36 Simple Dermatographism (Urticaria Factitia) Management: Symptom avoidance Avoid mechanical irritation, toweling after showering, light nonirritating clothing Second generation antihistamines (high doses) Leukotriene antagonists and/or H2 blockers Cyclosporin Omalizumab Narrow-band UV-B (need clinical trials)
37 Cholinergic Urticaria Up to 30% of cases of PU Lesions following a rise in body temperature (ie: exercise, hot bath) Symptoms decrease with age and eventually disappear Itchy, pinpoint wheals mostly on the limbs and trunk Last 15 to 60 minutes
38 Cholinergic Urticaria May also be induced by emotional stress and spicy foods and beverages May be due to antibodies to sweat Provocation testing: Moderate exercise on the treadmill to the point of sweating and 15 minutes beyond If the test is positive, passive warming test next (bath 42C) Passive warming differentiates from exercise induced urticaria/anaphylaxis Management: Avoidance 2 nd generation anti-histamines Desensitization protocols (regular exercise for eg.) Omalizumab Scopolamine Propanolol, anti-histamines, montelukast
39 Delayed Pressure Urticaria Up to 1/3 of cases of PU (common in CU) Angioedema at sites of exposure to sustained pressure to the skin (belts, purse), usually with a few hours delay (6 to 8) Frequently associated with severe burning and pain Flu-like symptoms, malaise, arthralgia
40 Delayed Pressure Urticaria Proinflammatory cytokines, TNF etc. may be involved Provocation Testing: Apply pressure to the skin using weighted rods or a dermographometer Shoulder, upper back, things or volar survace of the forearm
41 Delayed Pressure Urticaria Postive test = red palpable swelling 6 hours later Threshold testing
42 Delayed Pressure Urticaria Management: Avoid mechanical pressure where possible Some reports of dapsone and sulfasalazine Non-sedating antihistamines High dose may be required (up to 4 times) Anti-leukotrienes have been tried
43 Cold-Induced Urticaria 5 to 30% of all PU Affects 2 sexes equally Release of inflammatory mediators after skin exposure to cold Occur within a few minutes of exposure Occur only in exposed areas Extensive cold contact ie: swimming may lead to systemic reactions (anaphylaxis)
44 Cold-Induced Urticaria May last from 5 to 8 years Provocation testing: Melting ice-cube in a thin plastic bag on the volar forearm for 5 minutes Assess response 10 minutes later Positive if test shows a palpable, visible wheal Usually pruritic and burning Threshold testing Management: Avoid ice-cold drinks Avoid very cold swimming pools/lakes Swim with a friend Prevention with 2 nd generation anti-histamines Usually higher than standard doses
45 Cold Induced Urticaria
46 Cold-Induced Urticaria Omalizumab, etanercept, anakinra Desensitization Decreasing the temperature of showers Maintenance through daily showers at lower temperature
47 Aquagenic Urticaria Rare < 100 cases described More common in women Onset after puberty Treatment with 2 nd generation antihistamines
48 Heat Contact Urticaria Rare (less than 100 cases described) Wheal after contact with temperatures that exceed those of the skin Lesions come a few minutes after exposure and resolve after 1 to 3 hours
49 Heat Contact Urticaria Provocation Testing: Local heat testing for 5 minutes at 45C Assess in 10 minutes Management: 2nd generation antihistamines Omalizumab (for difficult to treat patients)
50 Solar Urticaria/Vibratory Urticaria Solar Rare Whealing on exposure to UV light Systemic reactions can occur Prevention with 2 nd generation anti-histamines Desensitization Vibratory Rare Skin swellings and itching after exposure to vibration 2 nd generation antihistamines IVIG?
51 Exercise-Induced Urticaria/Anaphylaxis 5 to 15% of all cases of anaphylaxis Induced by exercise with or without food (but not passive warming like Cholinergic urticaria) More common in atopic individuals Typical symptoms of anaphylaxis: pruritis, urticaria, angioedema, flushing, shortness of breath etc.
52 Exercise-Induced Urticaria/Anaphylaxis Provocation Testing: Exercise on treadmill supervised If food dependent suspected, NPO before one challenge but not the second Management: Avoid exercise in cold, hot or humid weather Avoid NSAIDs Avoid exercising outside in pollen season if seasonal atopy Avoid allergen if relevant (3 hours before and 1 hour after) 2 nd generation antihistamines (?as prophylaxis) Epinephrine autoinjector Exercise with a friend
53 Summary (What did we accomplish?) Here is what we said we would do: 1. Discuss the differential diagnoses of both acute and chronic urticaria 2. Describe the work-up and management of various forms of acute and chronic urticaria 3. describe an approach to the physical urticarias and their management
54
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