Chronic Urticaria and Atopic Dermatitis in the Elderly

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1 WISC December 214 Rio de Janeiro, Brazil WAO International Scientific Conference (WISC) and the XLI (41 th ) Annual Meeting of the Brazilian Association of Allergy and Immunology (ASBAI) 22-3SY Chronic Urticaria and Atopic Dermatitis in the Elderly 11: AM - 12:3 PM, Sul America, Sala B1 Chronic Urticaria and Atopic Dermatitis in the Elderly Chairpersons:Dr Ignacio J. Ansotegui, Hospital Quiron Bizkaia, Spain Dr HaeRan Lee, South Korea, Korea COI Disclosure In relation to this presentation, I declare the following, real or perceived conflicts of interest: Research support from -GlaxoSmithKline -Japan Boehringer Ingelheim -Tanabe-Mitsubishi -Shionogi -Sanofi -Kyouwahakkou-Kirin -Novartis Pharma -Shimense Healthcare Consultancy fees from -GlaxoSmithKline -Sanofi -MSD Michihiro Hide, MD, Ph.D Department of Dermatology, Hiroshima University, Japan

2 Learning Objectives: 1.To know prevalence of atopic dermatitis and urticaria in elderly populations 2. To know clinical manifestations of atopic dermatitis and urticaria in elderly patients 3. To know prognosis of chronic urticaria and type I allergy developed in elderly ages 4. To know diagnosis of angioedema in elderly patients

3 Number of patients who visited Dermatology clinic - Nationwide study in Japan 1,2 1, (total number of patients in clinics studied) Atopic dermatitis Tinea pedis Urticaria and angioedema Total Japanese population 2 Age Depicted based on data reported by Furue M, et al. J Dermatol 38: 31-32, 211

4 Surveillance of atopic dermatitis by Web questionnaire Age of the subjects 2s 2-24 Prevalence of atopic dermatitis (selfreported) in Victoria, Australia Age:2 years Sex:M:F=48: Subjects number: 1,347 Prevalence (%) (Preregistered 25 for Web research) (Preregistered for Victoria Web population research) 2 Research 15 Have you ever period:214/mar/26-28 diagnosed as 1 Have atopic 5 you dermatitis? * ever diagnosed as atopic dermatitis? * No 85.5% Plunkett A, et al. Int J Dermatol 1999, 38, Age ( Male Femake) Yes 14.5% Have you ever diagnosed as atopic dermatitis? * *The question as been validated in comparison with questionnaire by UK working group 35% 3% 25% 2% 15% 1% 5% % 6s (24.5%) 6-38% (27.7%) % 5s % 5% % % % % Suffer from AD % 4s Under medical treatment (27.%) Age (21.%) (19.4%) 3s

5 Number of patients who consulted clinic for atopic dermatitis in Japan nation wide study based on questionnaire for general population 25 (x1,) Japanese population in 27 (x1/5,) Japanese population in 212 (x1/5,) Japanese population in 21 (x1/5,) 1 5 Age group

6 Number of patients who visited Dermatology clinic - Nationwide study in Japan 1,2 (total number of patients in clinics studied) (Cambridge, UK) Urticaria and angioedema 1, Champion, et al., Br J Derm 81: , 1969 Total Japanese population 2 Age Depicted based on data reported by Furue M, et al. J Dermatol 38: 31-32, 211

7 Prevalence of CSU in age groups and sex Prevalence of patients with CSU who visited Hiroshima University outpatient clinic (n=21) Prevalence of patients with CSU who visited Hiroshima University outpatient clinic (n=21) (adjusted with Japanese population in 26) 25 Men 2 Female 25 Men 2 Female % 1 % The analysis of out patients clinic in Hiroshima University revealed the prevalence of CSU is low in elderly people.

8 Clinical manifestations of atopic dermatitis in elderly patients 1 61 y-old F 1-3 are courtesy of Dr Tanei (Tokyo Metropolitan Geriatric Hospital, Japan) 2 79 y-old M 3 61 y-old F 3 77 y-old F 4 77 y-old F Eczematous dermatitis predominantly in the face, neck, trunk, extensor and flexure site of extremities but less commonly in the antecubital and popliteal areas.

9 Clinical manifestations of atopic dermatitis in elderly patients Tanei R and Katsuoka K. J Dermatol, 28; 35: Diagnosed 16 patients as AD out of 4,1 cases of aged ( 65 years old) patients with various types of eczema and dermatitis (.39%). M:F=3:1 Eczematous dermatitis was observed predominantly in the face, neck, trunk, extensor and flexure site of extremities, but less commonly in the antecubital and popliteal areas. Total serum IgE: 8,81±13,511 IU/ml (5~53,65) Four of them were relatively low: 5, 16, 574, 714 IU/ml Skin biopsy revealed the increase of mast cells and dermal dendritic cells bearing IgE

10 Immunohistological manifestations of atopic dermatitis in elderly patients Tanei R, et al. JEADV, 213; 27: Mast cell tryptase IgE Atopic (extrinsic) dermatitis Double staining of IgE (red) and CD11c (green) Atopic dermatitis Non-atopic eczema Non-atopic (asteatotic) eczema Merge Merge IgE CD11c DAPI IgE CD11c DAPI Mast cell and IgE + cell infiltration is increased in a lichenified skin lesion of a patients with extrinsic elderly AD. Coexistence of IgE-bearing mast cells (red), dermal dendritic cells (green) and IgE-bearing dermal dendritic cells (yellow). Courtesy of Dr Tanei (Tokyo Metropolitan Geriatric Hospital, Japan)

11 Urticaria observed in elderly patients 67yr M Anaphylaxis 8yr F CSU 76yr Acute U 69yr F CSU 69yr M CSU 84yr M Mechanical U

12 Percentage of patients with CSU whose symptoms were not sufficiently suppressed by a standard dose of antihistamine in Hiroshima University Hospital (%) % <1 1-<2 2-<3 3-<4 4-<5 5-<6 6-<7 7-<8 8- Prevalence of CSU in age groups adjusted by whole Japanese population <1 1-<2 2-<3 3-<4 4-<5 5-<6 6-<7 7-<8 8- The prevalence of urticaria is low, but the population of refractory cases among age group is similar or even worse in elderly patients

13 Prognosis of patients with CSU, not sufficiently responded to a standard dose of antihistamines Remission rates (%) <16 years-old n=1 P<.5 16 years-old n=17 Remission rates (%) 1 < 6 years old (n=95) 6 years or more (n=22) Follow-up periods (months) Follow-up periods (months) The improvement rate of <6 years-old patients appears to be slightly higher, but the difference was not significant. Hiragun M, et al. Allergy 68: , 213

14 Time course of acquired type I allergy against hydrolyzed wheat antigens From to 25 to 21, approximately 46.5 million soap cakes containing hydrolyzed wheat protein have been sold in Japan and more than 2, individuals have been identified as sensitized with the wheat protein.

15 Time course of acquired type I allergy against hydrolyzed wheat antigens Remission rates (%) < 3 years old 3 years old or more **P=.67 (n=18) (n=85) Remission rates (%) 1 5 < 6 years old (n=81) 6 years old or more (n=22) P= Remission rates (%) < 5 years old (n=65) 5 years old or more (n=38) P=.292 Remission rates (%) < 65 years old (n=92) 65 years old or more(n=11) P= Months Months Type I allergy acquired in old age tends to be prolonged

16 Surveillance of atopic dermatitis by Web questionnaire 1% 9% Disease severity (POEM) 2% Steroid phobia 8% 16% 7% 6% 5% 4% mild~moderate severe most severe 12% 8% 3% 2% 4% 1% % 2~29 3~39 4~49 5~59 6~ % 2~29 3~39 4~49 5~59 6~ Atopic dermatitis in elderly patients tends to be mild and patients tend to be less steroid-phobic as compared with younger populations of the patients.

17 Clinical manifestations of atopic dermatitis in elderly patients Age of onset and association with atopic diathesis 5 n= IgE-allergic Non-IgE-allergic Data were kindly provided by Dr Tanei R (Tanei R. J Clin Med, in press) The onset of AD was at 6 years old or later in 4% of the patients at 6.

18 Classification of angioedema 1. Bradykinin mediated C1-INH deficiency/defect Normal C1-INH Positive HAE-1 HAE-2 HAE with normal C1-INH Inheritance Negative Acquired angioedema due to C1-INH deficiency/consumption Drug-induced angioedema (eg, ACEI) Non-classified angioedema 2. Mast cell mediated, normal C1-INH IgE mediated Non-IgE mediated Anaphylaxis IgE-mediated urticaria Chronic spontaneous urticaria Inducible urticarias Non-classified angioedema 3. Idiopathic, normal C1-INH, negative inheritance Non-classified angioedema Lang DM, et al. International consensus on hereditary and acquired angioedema. Ann Allergy Asthma Immunol 19: , 212

19 Angioedema may be induced and/or exacerbated by either decrease of C1-INH or ACE inhibitor Kinin system Prekallikrein HMW- Kininogen Inactivated peptides Kallikrein C1-INH C1-INH Bradykinin Kininase II (ACE) ACE inhibitor Activation Inhibition ACE inhibitor may not induce angioedema immediately after the intake of medication, but after a certain duration, such as a few days, weeks, or months. The risk of ARB cannot be totally excluded, but much lower than that of ACE inhibitor. Bradykinin receptor 2 Angioedema C1-INH activity may decrease by autoantibody against C1-INH or consumption by lymph-proliferative diseases

20 24 時間後 7-year-old male. Tongue swelling on the 5 th day of the treatment with lisinopril(1). No effect of corticosteroid and antihistamine. BP=2/9mmHg Risk factors (odds ratio): -black race (2.88) -history of drug rash (3.78) -age > 65 years (1.6) -seasonal allergies (1.79)

21 Summary 1. The prevalence of AD and urticaria in elderly populations is low at present. 2. However, elderly patients with AD may increase either by non-remittance of young adults or the increase of old age onset in future. 3. Elderly AD preserves many characteristics observed in young patients, but tends to mild and avoid eruptions in cubital and popliteal regions. 4. Populations of refractory case in CSU are the same (ca. 6%) throughout the age up to 8, but diminished in patients in 8s or older. 5. On the other hand, type I allergy obtained at old age tends to remain for longer than that in young age. 6. The risk of developing angioedema by continuous use of ACE-I is higher (odds ratio: 1.6) in >65 years old and should be avoided, especially those with HAE and/or lymphoproliferative diseases.