• Share
  • Email
  • Embed
  • Like
  • Save
  • Private Content
Chronic idiopathic urticaria; background & clinical presentation
 

Chronic idiopathic urticaria; background & clinical presentation

on

  • 1,106 views

Chronic idiopathic urticaria; background & clinical presentation

Chronic idiopathic urticaria; background & clinical presentation

Presented by Watt Mitthansiri, MD.

August 2, 2013

Statistics

Views

Total Views
1,106
Views on SlideShare
1,105
Embed Views
1

Actions

Likes
1
Downloads
35
Comments
0

1 Embed 1

http://translate.googleusercontent.com 1

Accessibility

Upload Details

Uploaded via as Microsoft PowerPoint

Usage Rights

© All Rights Reserved

Report content

Flagged as inappropriate Flag as inappropriate
Flag as inappropriate

Select your reason for flagging this presentation as inappropriate.

Cancel
  • Full Name Full Name Comment goes here.
    Are you sure you want to
    Your message goes here
    Processing…
Post Comment
Edit your comment

    Chronic idiopathic urticaria; background & clinical presentation Chronic idiopathic urticaria; background & clinical presentation Presentation Transcript

    • Chronic Idiopathic Urticaria Episode 1: Background and clinical presentation Wat Mitthamsiri, M.D. Allergy and Clinical Immunology Unit Department of Medicine King Chulalongkorn Memorial Hospital
    • Outline • Urticaria: General information • Chronic idiopathic urticaria – Epidemiology – Pathophysiology – CIU and other conditions – Clinical presentation • Investigation & management : To be continued in next episode.
    • Urticaria Definition
    • Urticaria • Recurrent wheals – Usually pruritic – Pink-to-red edematous plaques – Often have pale centers. • The wheals are transient, mostly last for <24 hours. Allen P Kaplan, Middleton’s Allergy: Principles and Practice 7th edition, 2009: 1063-1081.
    • Urticaria • The appearance of pruritic, erythematous, cutaneous elevations that blanch with pressure, indicating the presence of dilated blood vessels and edema T. Poonawalla, et al. Am J Clin Dermatol 2009; 10(1); 9-21
    • Urticaria • The sudden appearance of wheals and/or angioedema • Wheal consists of 3 typical features: – A central swelling of variable size – Almost invariably surrounded by a reflex erythema – Associated itching or burning sensation – A fleeting nature – Skin returning to its normal appearance, usually within 1–24 h EAACI/GA2LEN/EDF/WAO guideline: definition, classification and diagnosis of urticaria, Allergy 2009: 64: 1417–1426
    • Urticaria Classification
    • Urticaria: Classification • By duration – Acute: • Wheals occurring for <6 weeks, – Chronic: • Any pattern of recurrent urticaria occurring at least twice a week for at least 6 weeks • The development of cutaneous wheals that occur on a regular basis (usually daily) for >6 weeks with individual lesions lasting from 4 to 36 hours. T. Poonawalla, et al. Am J Clin Dermatol 2009; 10(1); 9-21 Grattan C, et al. J Am Acad Dermatol 2002; 46: 645–657.
    • EAACI/GA2LEN/EDF/WAO guideline: definition, classification and diagnosis of urticaria, Allergy 2009: 64: 1417–1426
    • Urticaria: Classification • By etiology – Drug reactions – Foods or food additives – Inhalation, ingestion of, or contact with antigens Allen P Kaplan, Middleton’s Allergy: Principles and Practice 7th edition, 2009: 1063-1081.
    • Urticaria: Classification • By etiology – Transfusion reactions – Infections: • Bacterial • Fungal • Viral • Helminthic Allen P Kaplan, Middleton’s Allergy: Principles and Practice 7th edition, 2009: 1063-1081.
    • Urticaria: Classification • By etiology (continued) – Insects (papular urticaria) – Collagen vascular diseases • Cutaneous vasculitis • Serum sickness – Malignancy: • Angioedema with acquired C1and C–1 inactivator (C–1 INH) depletion Allen P Kaplan, Middleton’s Allergy: Principles and Practice 7th edition, 2009: 1063-1081.
    • Urticaria: Classification • By etiology (continued) – Physical urticarias • Cold urticaria • Cholinergic urticaria • Dermographism • Pressure urticaria (angioedema) • Vibratory angioedema • Solar urticarial • Aquagenic urticaria Allen P Kaplan, Middleton’s Allergy: Principles and Practice 7th edition, 2009: 1063-1081.
    • Urticaria: Classification • By etiology (continued) – Urticaria pigmentosa: systemic mastocytosis – Hereditary diseases • Hereditary angioedema • Familial cold urticaria • C3b inactivator deficiency • Amyloidosis with deafness and urticaria (Muckle-Wells syndrome) Allen P Kaplan, Middleton’s Allergy: Principles and Practice 7th edition, 2009: 1063-1081.
    • Urticaria: Classification • By etiology (continued) – Chronic autoimmune urticaria and angioedema • (40-45% of chronic urticaria) – Chronic idiopathic urticaria and angioedema • (55-60% of chronic urticaria) – Idiopathic angioedema Allen P Kaplan, Middleton’s Allergy: Principles and Practice 7th edition, 2009: 1063-1081.
    • Urticaria: Classification EAACI/GA2LEN/EDF/WAO guideline: definition, classification and diagnosis of urticaria, Allergy 2009: 64: 1417–1426
    • Chronic Idiopathic Urticaria (CIU) Epidemiology
    • Epidemiology • Various incidence reports from 20-90% in all chronic urticaria • This condition is thought to affect at least 0.1% of the population Allen P Kaplan, Middleton’s Allergy: Principles and Practice 7th edition, 2009: 1063-1081. Greaves MW. N Engl J Med 1995; 332: 1767–1772.
    • Epidemiology • 79% from 554 urticarial patients between 1956-1967 in a hospital in Cambridge • 76% (1,657 out of 2,350 cases) in 32 years in a review in 1988 Champion RH. Br J Dermatol 1988; 119: 427–436. Champion RH, et al. Br J Dermatol 1969; 81: 588–597.
    • Epidemiology: Thailand • A retrospective report from Department of Dermatology, Siriraj Hospital, during 2000–2004. • From total of 450 patients with chronic urticaria, 337 patients (75%) were diagnosed as CIU – 66 were male (20%) – 271 were female (80%) – Mean age = 34 years (range: 15–80 years) K. Kulthanan et al. J Derm 2007; 34: 294–301
    • K. Kulthanan et al. J Derm 2007; 34: 294–301
    • K. Kulthanan et al. J Derm 2007; 34: 294–301
    • Chronic Idiopathic Urticaria (CIU) Pathophysiology
    • Pathophysiology • Gross Allen P Kaplan, Middleton’s Allergy: Principles and Practice 7th edition, 2009: 1063-1081.
    • Pathophysiology • Gross – Infiltrative hives – With palpably elevated borders that vary in size or shape – But generally are rounded Allen P Kaplan, Middleton’s Allergy: Principles and Practice 7th edition, 2009: 1063-1081.
    • Pathophysiology • Microscopic Allen P Kaplan, Middleton’s Allergy: Principles and Practice 7th edition, 2009: 1063-1081.
    • Pathophysiology • Microscopic – Non-necrotizing perivascular mononuclear cell infiltrate (mainly T helper lymphocytes) – Occasional prominent eosinophil accumulation – Only skin biopsy in patients with delayed pressure urticaria that is virtually indistinguishable chronic urticaria Allen P Kaplan, Middleton’s Allergy: Principles and Practice 7th edition, 2009: 1063-1081. Mekori Y, et al. J Allergy Clin Immunol 1983; 72(6):681–684.
    • Pathophysiology • Microscopic – Elias et al, reported: • 50% T lymphocytes • No B cells • 20% monocytes • 10% mast cells • T cell subtype varied greatly and revealed no predominant pattern Elias J, et al. J Allergy Clin Immunol 1986; 78: 914–918.
    • Pathophysiology Elias J, et al. J Allergy Clin Immunol 1986; 78: 914–918.
    • Pathophysiology • Microscopic (continued) – 10-fold increase of mast cells – 4-fold increase of mononuclear cells – Circulating basopenia related perhaps to migration into skin Grattan C, et al. Clin Exp Allergy 1997; 27(12):1417–1424. Ying S, et al. J Allergy Immunol 2002; 109(4):694–700.
    • Pathophysiology • Increased skin mast cell • Increased histamine in blister fluid compared with fluid from normal control subjects • Increased total skin histamine content • But this is not consistent findings in all study Allen P Kaplan, Middleton’s Allergy: Principles and Practice 7th edition, 2009: 1063-1081. Nettis E, et al. Allergy 2001; 56(9):915.
    • Pathophysiology • In one report, the authors failed to indicate an increased number of mast cells • They hypothesized that there might be: – Increase in number of basophils – Increase in histamine content in each cell • But it has not been proved Smith C, et al. J Allergy Clin Immunol 1995; 96(3):360–364.
    • Pathophysiology • Eosinophil major basic protein deposition in skin found in half of patients • But only a fraction of the patients had obvious eosinophil infiltration Peters M, et al. J Invest Dermatol 1983; 81(1):39–43.
    • Pathophysiology • Early lesions: Neutrophil found along with infiltration of eosinophils • More intense inflammatory infiltrate in patient with positive IgE receptor Ab • Combination of neutrophils, eosinophils, CD4+ lymphocytes, and monocytes resembled a cutaneous late-phase reaction Sabroe R, et al. J Allergy Clin Immunol 1999; 103:484–493.
    • Chronic Idiopathic Urticaria (CIU) Associated conditions
    • CIU and Allergy • No increased incidence of: – Eczema – Allergic rhinitis – Asthma – Compared with person without chronic urticaria • The IgE levels of patients are within normal limits Allen P Kaplan, Middleton’s Allergy: Principles and Practice 7th edition, 2009: 1063-1081.
    • CIU and Allergy • A report of chronic urticaria cases from Thailand found that: – Prevalence of atopy was not increased – Symptomatic dermographism found in 3.8% of patient • An increased incidence of dermographism from 8–22% found in patients with chronic urticaria Gorevic PD, et al. Int J Dermatol 1980; 19: 417–435. K. Kulthanan et al. J Derm 2007; 34: 294–301
    • CIU and Infection • Various infections have been reported to be the associating factors of CU: – Parasitic infection – Hepatitis – H. pyroli • Concurrent infections can exacerbate the condition • In most cases, treatments of infections does not improve urticarial symptoms K. Kulthanan et al. J Derm 2007; 34: 294–301
    • CIU and Autoimmunity • Autoimmune hypothyroidism (Hashimoto’s thyroiditis) – Association found with the presence of peroxidase or thyroglobulin Ab. – Incidence: 12–14% – 24% incidence of antithyroglobulin Ab or antimicrosomal Ab or both, found in patients with chronic urticaria Kikuchi Y, et al. J Allergy Clin Immunol 2003; 112(1):218. Leznoff A, et al. Arch Dermatol 1983; 119(8):636–640. Leznoff A, et al. J Allergy Clin Immunol 1989; 84(1):66–71.
    • CIU and Autoimmunity • Autoimmune hypothyroidism (Hashimoto’s thyroiditis) But… – Thyroid status did not relate to the occurrence of urticaria – Hives persist even with euthyroid achievement – Autoantibodies persist also Allen P Kaplan, Middleton’s Allergy: Principles and Practice 7th edition, 2009: 1063-1081.
    • CIU and Autoimmunity • CIU and autoimmune hypothyroidism in Thai From 100 patients + 100 volunteers studied – 21 cases with CIU: positive for thyroid Ab (vs 9 cases in volunteers) – 9 cases: negative for thyroid Ab when repeating the tests after 3 months – 12 patients still had persistent elevation of Ab after 3 months Kullavanijaya P, et al. J Med Assoc Thai 2002 Aug; Vol. 85 (8), pp. 901-6.
    • CIU and Autoimmunity • CIU and autoimmune hypothyroidism in Thai TFT was performed in 12 patients with persistent elevation of Ab. – 9 cases had autoimmune thyroiditis with euthyroidism – 1 case had subclinical hyperthyroidism – 1 case had autoimmune hyperthyroidism – 1 case had subclinical hypothyroidism Kullavanijaya P, et al. J Med Assoc Thai 2002 Aug; Vol. 85 (8), pp. 901-6.
    • CIU and Autoimmunity • 10% incidence of circulating IgG or IgM anti-IgE Ab found in subjects with chronic urticaria and occasionally cold urticaria • Hypothesis: Ab stimulate cutaneous mast cells degranulation and lead to – Acute hives – Late-phase reaction – Cellular infiltration Gruber B, et al. J Invest Dermatol 1988; 90(2):213–217.
    • CIU and Autoimmunity • Anti-IgE receptor Ab found in 30–40% of patients • An additional 10% of patients with anti-IgE Ab • These studies demonstrated autoreactivity to autologous serum (injections of serum into the patient induced a hives) Hide M, et al. N Engl J Med 1993; 328(22):1599–1604. Allen P Kaplan, Middleton’s Allergy: Principles and Practice 7th edition, 2009: 1063-1081.
    • CIU and Autoimmunity Becky M. et al. Current Allergy and Asthma Reports 2005, 5:270–276
    • CIU and Autoimmunity • Reactivity with the α-subunit of IgE receptor was confirmed in about 40% of patients • Demonstrated by using activated rat basophil leukemia cells transfected with – α-subunit of the IgE receptor – Human basophils – Cutaneous mast cells Allen P Kaplan, Middleton’s Allergy: Principles and Practice 7th edition, 2009: 1063-1081.
    • CIU and Autoimmunity • IgG anti-α Ab might give a role for complement to augment histamine release • Role of C5a is demonstrated: – Activation of the classical complement pathway +Cross-linking of the IgE receptor by autoAb =Chemotactic for neutrophils, eosinophils, and monocytes -> infiltration occured Allen P Kaplan, Middleton’s Allergy: Principles and Practice 7th edition, 2009: 1063-1081.
    • CIU and Autoimmunity • Pathogenic autoAb: IgG1 and/or IgG3 • IgG4 is rarely contributory • IgG2 anti-α does not lead to basophil histamine release • IgG2 caused false-positive immunoblots Soundararajan S, et al. J Allergy Clin Immunol 2005; 115(4):815–821.
    • CIU and Autoimmunity • Presence of IgG antibody to the low- affinity IgE receptor on eosinophils (CD23) – Degranulation of eosinophils – Activation of basophils and maybe mast cells by eosinophil cationic proteins Puccetti A, et al. I Clin Exp Allergy 2005; 35(12):1599–1607.
    • CIU and Autoimmunity • Hyporesponsiveness of basophils of chronic urticaria patients upon stimulation with anti-IgE was demonstrated long time ago • But hyperresponsiveness of basophil to autologous serum was found: – In either patients with or without autoantibody (idiopathic) Luquin E, et al. Clin Exp Allergy 2005; 35(4): 456–460. Allen P Kaplan, Middleton’s Allergy: Principles and Practice 7th edition, 2009: 1063-1081.
    • CIU and Autoimmunity • Basophils from chronic urticaria patients are either hypo-or hyperresponsive to stimuli • Suggesting abnormality in signal transduction? – ‘Ras’-related pathways of MAP kinase activation – Abnormality to increased levels of ‘SHIP’ Vonakis B, et al. J Allergy Clin Immunol 2007; 119(2):441–448. Confino-Cohen R, et al. J Allergy Clin Immunol 2002; 109(2):349–356.
    • Incomplete jigsaw • From mentioned data: – Perivascular infiltrate in chronic urticaria should be a late-phase reaction – Or at least a variant of it • But there is still some discrepancies (as some examples in next 2 slide) Allen P Kaplan, Middleton’s Allergy: Principles and Practice 7th edition, 2009: 1063-1081.
    • Incomplete jigsaw Allen P Kaplan, Middleton’s Allergy: Principles and Practice 7th edition, 2009: 1063-1081.
    • Incomplete jigsaw Allen P Kaplan, Middleton’s Allergy: Principles and Practice 7th edition, 2009: 1063-1081. Issues Late phase reaction CIU Basophil -More prominent in nose lung and skin -Less prominent Eosinophil -Very prominent in asthma and nasal polyp -Induce or cause late phase reaction -Vary from none to very prominent in the lesion Monocyte -Minimally elevated -Markedly elevated (up to 20%) Lymphocyte -Less prominent -Th2 predominance in atopy -More prominent -No Th2
    • Incomplete jigsaw • Why the reaction is limited only to mast cell in the skin? • Complement-mediated activation via C5a has been proposed to explain why only skin mast cells are triggered in CIU rather than mucosal mast cells which lack responsiveness to the C5a receptor Allen P Kaplan, Middleton’s Allergy: Principles and Practice 7th edition, 2009: 1063-1081. Becky M. et al. Current Allergy and Asthma Reports 2005, 5:270–276
    • Incomplete jigsaw • OK, then why autoAb may act only in some distinct regions of the skin? • What about most CIU subjects who lack autoantibodies or histamine- releasing activity (HRA)? • Obviously we need more explanation Becky M. et al. Current Allergy and Asthma Reports 2005, 5:270–276
    • Without autoimmunity • In antibody-negative subjects • There is evidence of other histamine- releasing factors acting on both mast cells and basophils – Cytokines – Complement components • Suggesting great heterogeneity in serum HRA Becky M. et al. Current Allergy and Asthma Reports 2005, 5:270–276
    • Chronic Idiopathic Urticaria (CIU) Clinical course
    • Clinical course • 47% of 78 patients with CIU had remission within 1 year • 32% of 86 patients with CIU, the symptoms were resolved after a 3-year • No difference in the natural course of: – Urticaria alone – Angioedema alone – Urticaria with angioedema Quaranta JH, et al. Ann Allergy 1989; 62: 421–424. Kozel MM, et al. J Am Acad Dermatol 2001; 45: 387–391.
    • Clinical course • The retrospective report from Siriraj: The only Thai report available in PubMed and MedLine database K. Kulthanan et al. J Derm 2007; 34: 294–301
    • Clinical course • From 337 patients with CIU in that report – 66 were male (20%) – 271 were female (80%) – Mean age = 34 years (range: 15–80 years) – Anti-thyroglobulin Ab positive: 16% – Anti-microsomal Ab positive: 12% K. Kulthanan et al. J Derm 2007; 34: 294–301
    • Clinical course • In 61 patients – ASST had been done to detect the autoAb to a high affinity IgE receptor (FCε RIα) on the mast cell surface – 15 patients (24.5%) had positive ASST results • So…they were diagnosis of autoimmune urticaria K. Kulthanan et al. J Derm 2007; 34: 294–301
    • Clinical course • CIU patients: – 34.5% were free of symptoms after 1 year – Median disease duration: 390 days • Autoimmune urticaria patients: – 56.5% were free of symptoms after 1.2 years – Median disease duration: 450 days K. Kulthanan et al. J Derm 2007; 34: 294–301
    • K. Kulthanan et al. J Derm 2007; 34: 294–301 CIU CAU
    • Pruritus • A study in 100 patients with CIU – Mean(+/-SD) clinical course = 30.2(+/- 53) months (range 2–384) Frequency of attack – 68 patients had daily pruritus – 23 patients had >/= 1 pruritus/wk G.Yosipovitch, et al. British Journal of Dermatology 2002; 147: 32–36.
    • Pruritus • A study in 100 patients with CIU Attacking time of the day – 25 patients had pruritus in the morning – 18 patients had pruritus at noon – 37 patients had pruritus in the evening – 46 patients had pruritus in the night G.Yosipovitch, et al. British Journal of Dermatology 2002; 147: 32–36.
    • Pruritus • A study in 100 patients with CIU Related symptoms – Heat sensation (n=45) – Sweating (n=15) – Pain (n=9) G.Yosipovitch, et al. British Journal of Dermatology 2002; 147: 32–36.
    • Pruritus • A study in 100 patients with CIU Location of pruritus – Arms (n=86) – Back (n=78) – Legs (n=75) – Scalp (n=13) – 13 patients had symmetrical pruritus G.Yosipovitch, et al. British Journal of Dermatology 2002; 147: 32–36.
    • Pruritus • Effects of daily activities on pruritus G.Yosipovitch, et al. British Journal of Dermatology 2002; 147: 32–36.
    • Pruritus • Effects of pruritus on quality of life – Sleep • 64 patients were woken by their itch • 62 paitents had difficulty falling asleep. – Mood • 52 patients: more agitated • 43 patients: difficulty in concentrating • 14 patients: being depressed. G.Yosipovitch, et al. British Journal of Dermatology 2002; 147: 32–36.
    • Pruritus • Effects of pruritus on quality of life – Diet • 34 patients: change in eating habits • 9 patients: special diet to relieve their itch – Sexual life • 33 patients: Reduction in sexual desire • 27 had reduced sexual function G.Yosipovitch, et al. British Journal of Dermatology 2002; 147: 32–36.
    • Take Home Message • Urticaria is a common skin condition • Urticaria is classified by duration of of symptom as acute (<6 wk) and chronic (>6 wk) • There are a lot of possible etiology that causes urticaria
    • Take Home Message • In chronic urticaria, mostly, etiology can’t be identified, so it’s labeled as chronic idiopathic urticaria (CIU) • Pathophysiology of CIU is not completely understood • CIU can seriously affect the patient’s quality of life.
    • Chronic Idiopathic Urticaria Episode 2: Investigation and Management -To be continued-