慢性特發性蕁麻疹

(1)

704 138

E E

E

( Chronic idiopathic urticaria ) ( Autoimmune urticaria )

Anti-Fc RI ( E )

( Thyroid autoimmunity )

( )

( urt icaria ) h i v e s n e t t l e r a s h

( w h e a l ) ( family Urticaceae/nettle family )

( Urtica thunbergiana )

(2)

( Laportea pterostigma )

( )

1

( i diopathic )

( physical urt icaria )

( chronic idiopat hi c urticaria, CIU )

( basophil )

( dermal mast cell ) E

( high affinity IgE receptor Fc RI ) - a n t i - Fc RI antibodies

²

(

) E ( IgE )

-anti-IgE antibodies

^{3 , 4}

( )

( mediator )

(aut oimmune urticaria )

^{5 , 6}

C I U

7 , 8

( H e l i c o -

bacter pylori )

⁹

w h e a l - a n d - f l a r e

( )

wheal ( )

flare ( ) ( axon

reflex )

( angioedema )

2 4

( urticari- al vascul itis )

( SLE ) ( Sjogre n's syn-

drome ) ( cryogl obuli nemia )

1 0

( type I/immediate-type hypersensitivity )

I g E ( cross-

l ink )

I g E - Fc R I

C I U

F c R I

w h e a l - a n d - f l a r e

1 9 8 6 G r a t t a n C I U

( autologous serum ) ( intra-

dermal injection ) w h e a l - a n d - f l a r e

11

-

( autologous serum skin test, ASST ) C I U

1 2

( histamine releas- ing factors )

C I U

G ( IgG )

1 3

H i d e 1 9 9 3

Fc R I ( recombinant soluble alpha

chain of the Fc RI, sFc R I ) I g G

. .

(3)

I g E ( Fc RI )

- a n t i - Fc R I - I g E

1 4

I g E - a n t i - I g E

I g E I g E ( IgE

sensitized )

I g E

^{1 5}

( basophil histamine rel ease assay ) C I U

1 5

a n t i - F c R I ( Western blot )

( e nz yme -li nke d immunosorbent a ssay, ELISA )

^{1 6 , 1 7}

( SLE ) ( dermatomyositis )

( pemphigus vulgari s ) ( bull ous pemphigoid )

1 7

( intravenous immunogl obulin, IVIG )

1 8

( non-functional )

I g G 2 I g G 4

C I U I g G 1

I g G 3

^{1 7 , 1 9}

C I U

5 0 % 6 0 % A S S T

( 25%

40% )

⁵

3 5 % 4 0 % a n t i - F c R I 3 5 % 1 0 % a n t i - I g E

3 , 1 5 , 2 0

( gold standard )

⁴

A S S T

1 2

3 0

0.05 ml ( ) 0 . 0 5

m l ( 1 0 g / m l )

0.05 ml 3 0

1.5 mm

A S S T 8 0 %

( )

5 0 % 5 0 %

(

)

⁶

( mast cell-specific histamine releasing factor )

2 1

2

A S S T

2 2 , 2 3

- a n t i - Fc R I a n t i - I g E -

1 9 9 3 R o s e B o n a

^{2 4}

( 1 ) T

( 2 ) ( 3 )

C I U ( 1 ) C I U

A S S T

w h e a l - a n d - f l a r e

^{2 5}

( 2 )

C I U

^{2 6}

( 3 )

C I U

^{2 6 , 2 7}

2 4

C I U

( HLA ) H L A D R B 1 * 0 4

( DR4 ) DQB1*0302 ( DQ8 ) C I U

2 8

C I U

(4)

C I U ( antithyroid antibodies, ATAs )

7 , 8

a n t i - thyroglobulin ( anti-TG ) a n t i - t h y r o p e r o x i d a s e / microsomal ( anti-TPO ) L e z n o ff

1 9 8 3 m i c r o s o m a l

1 2 % 5 . 6 %

^{2 9}

Tu r k t a s

11 . 7 % a n t i - T G 9 . 5 7 % m i c r o s o-

m a l 3 . 7 %

3 0

G a i g C I U 1 4 . 7 %

3 1

Z a u l i 1 2 2 C I U

3 5 ( 29% ) a n t i - T G a n t i - T P O anti-TSH re-

c e p t o r 1 4

( T S H )

^{3 2}

A s e r o 2 5 7 6 6

( 26% ) 4 6

1 6 4

3 3

Ve r n e u i l 4 5 3 0

2 6 . 7 % 3 . 3 %

3 4

To u b i 1 3 9

1 7 ( 12% ) ( )

( p=0.004 )

^{3 5}

1 2 % 2 9 %

( 1% 10% )

8

Ve r n e u i l

(

)

^{3 4}

K a n d e e l C I U

( Hashimoto thyroiditis )

3 6

To u b i

2 4 7 0 %

5 0 %

5 2 % 1 6 %

3 5

5 0 7 0

8 0

7

L a n i g a n A 5 0

B 5 0

C 5 0

A 2 8 %

B C 4 % 6 %

A B C

( thyroid autoimmunity )

^{3 7}

a n t i - Fc R I (

A S S T )

K i k u c h i

2 8 2

2 7 . 7 %

10.9% ( p<0.001 )

a n t i - Fc R I

^{3 8}

F u s a r i 8 2

A S S T 6 2 %

A S S T 3 9 %

( p>0.05 ns ) 2 8 A S S T

( 14 ) ASST

1 5 1 3

A S S T ( 86.7% )

1 3 1 ( 8 % ) A S S T

( p<0.001 )

^{3 9}

I g E

7 , 8

(5)

( thyroxine ) ( euthyroid )

4 0 , 4 1

4 7 %

4 2

8

A B ( pre-icteric

phase )

^{4 3 , 4 4}

A

B

8 5 1 7 . 6 % B

5 %

4 5

9 % B

4 6

C ( pre-icteric

phase )

^{4 7}

C

^{4 8}

2 1

5 8

^{4 9}

2 4 %

C ( anti-HCV )

22% C R N A 1 6 9 2

C 1 . 1 %

C C

0 2 %

5 0 - 5 4

( He li cobac ter pylori )

( m ol e c u l a r

mimicry )

⁹

We d i

9 1 % 5 0 %

5 5

Di Ca mpl i

a m o x i c i l l i n c l a r i t h r o m y c i n l a n s o-

p r a z o l e 8 8 %

5 6

S c h n y d e r

( double-blind placebo-controlled crossover study )

4 6 1 2 a m o x i -

c i l l i n l a n s o p r a z o l e 3

1

^{5 7}

E r e l

3 9 2 9

5 8

2 0 0 3 F e d e r m a n

1 0 3 0 . 9 % 2 1 . 7 %

1 3 . 5 % ( odds ratio )

2.9 ( 95% 1 . 4 - 6 . 8 P =.005 )

5 9

/

H 1

/ H 1 ( H1 antihistamine/histamine H1 re- ceptor antagonist )

6 0

acrivastine ( Semprex ) cetiri zine ( Zyrtec ) desloratidine ( Clarinex ) fexodenadine ( Allegra ) levocetirizine ( Xyzal ) loratadine ( Clarityne ) m i z o l a s t i n e

c h l o r p h e n i-

r a m i n e diphenhydramine ( Benadryl) h y d r o x-

yzine ( Vistaril )

(6)

( A l l e g r a 240 mg )

6 , 6 0

H 2 H 2 ( flare )

H 1 H 2

6 1

H 1 H 2

H 2 H 1

H 1 H 1

H 2

^{6 0}

Doxepin ( Sinequan )

H 1 H 2

6 , 6 0

( leukotriene receptor an- tagonist )

m o n - t e l u k a s t z a f i r l u k a s t 3 0

C I U

( single blind placebo-controlled crossover study ) m o n t e l u k a s t c e t i r i z i n e c e t i r i z i n e

c e t i r i z i n e

^{6 2}

d e s l o r a t a d i n e m o n t e l u k a s t d e s l o r a t a d i n e m o n-

t e l u k a s t d e s l o-

r a t a d i n e m o n t e l u k a s t

6 3

z a f i r l u k a s t

c e t i r i z i n e z a f i r l u k a s t z a f i r l u k a s t A S S T

A S S T z a f i r -

l u k a s t

^{6 4}

z a f i r l u k a s t z a f i r-

l u k a s t

^{6 5}

H 2 H 1

3 0 p r e d n i s o l o n e

6 0

6 6

c y -

closporin ( ) 3 0

A S S T

2 0 c y c l o s p o r i n 1 9

A S S T 5

2 0

^{6 7}

c y - c l o s p o r i n

^{6 8}

C y c l o s p o r i n

2.5~5 mg/kg/day

G r e a v e s

c y c l o s p o r i n

⁶

c y c l o s p o r i n t a c r o l i m u s m e t h o t r e x a t e h y d r o x y c h l o r o q u i n e

6 9 - 7 1

( i n t r a - ve nous immunogl obul in, IVIG )

( plasmapheresis )

^{2 6 , 2 7}

A n t i - Fc R I a n t i - I g E

7 2

(7)

7 3

1.Zuberbier T, Greaves MW, Juhlin L, et al. Definition, classifi- cation, and routine diagnosis of urticaria: a consensus report. J Investig Dermatol Symp Proc 2001; 6: 123-7.

2.Sheikh J. A utoantibodies to the high-affinity IgE receptor in chronic urticaria: how important are they? Curr Opin Allergy Clin Immunol 2005; 5: 403-7.

3.Kaplan AP. Chronic urticaria: pathogenesis and treatment. J Allergy Clin Immunol 2004; 114: 465-74.

4.Greaves M. Autoimmune urticaria. Clin Rev Allergy Immunol 2002; 23: 171-83.

5.Grattan C. Autoimmune urticaria. Immunol Allergy Clin North Am 2004; 24: 163-82.

6.Sabroe RA, Greaves MW. Chronic idiopathic urticaria with func- tional autoantibodies: 12 years on. Br J Dermatol 2006; 154:

813-9.

7.Dreskin SC, Andrews KY. The thyroid and urticaria. Curr Opin Allergy Clin Immunol 2005; 5: 408-12.

8.Doutre MS. Chronic urticaria and thyroid auto-immunity. Clin Rev Allergy Immunol 2006; 30: 31-7.

9.Wedi B, Raap U, Kapp A. Chronic urticaria and infections. Curr Opin Allergy Clin Immunol 2004; 4: 387-96.

10.Grattan CE, Sabroe RA, Greaves MW. Chronic urticaria. J Am Acad Dermatol 2002; 46: 645-57.

11.Grattan CE, Wallington TB, Warin RP, Kennedy CT, Bradfield J W. A serological mediator in chronic idiopathic urticaria--a clinical, immunological and histological evaluation. Br J Dermatol 1986; 114: 583-90.

12.Sabroe RA, Grattan CE, Francis DM, et al. The autologous serum skin test: a screening test for autoantibodies in chronic idiopathic urticaria. Br J Dermatol 1999; 140: 446-52.

13.Grattan CE, Francis DM, Hide M, Greaves MW. Detection of circulating histamine releasing autoantibodies with functional properties of anti-IgE in chronic urticaria. Clin Exp Allerg y 1991; 21: 695-704.

14.Hide M, Francis DM, Grattan CE, Hakimi J, Kochan JP, Greaves MW. Autoantibodies against the high-affinity IgE receptor as a cause of histamine release in chronic urticaria. N Engl J Med 1993; 328: 1599-604.

15.Niimi N, Francis DM, Kermani F, et al. Dermal mast cell acti- vation by autoantibodies against the high affinity IgE receptor in chronic urticaria. J Invest Dermatol 1996; 106: 1001-6.

1 6 . Tong LJ, Balakrishnan G, Kochan JP, K inet JP, Kaplan AP.

Assessment of autoimmunity in patients with chronic urticaria.

J Allergy Clin Immunol 1997; 99: 461-5.

17. Fiebiger E , H ammerschmid F, Stingl G , Maurer D. Anti- FcepsilonRIalpha autoantibodies in autoimmune-mediated dis- orders. Identification of a structure-function relationship. J Clin

Invest 1998; 101: 243-51.

18. Hor n MP, Gerster T, O chensberger B, et al. Human anti- FcepsilonRIalpha autoantibodies isolated from healthy donors cross-react with tetanus toxoid. Eur J Immunol 1999; 29: 1139- 48.

19.Soundararajan S, Kikuchi Y, Joseph K, Kaplan AP. Functional assessment of pathogenic IgG subclasses in chronic autoimmune urticaria. J Allergy Clin Immunol 2005; 115: 815-21.

20.Sabroe RA, Fiebiger E, Francis DM, et al. Classification of an- ti-FcepsilonRI and anti-IgE autoantibodies in chronic idiopath- ic urticaria and correlation with disease severity. J Allergy Clin Immunol 2002; 110: 492-9.

21. Ase ro R, Lorini M, Chong SU , Z uberbier T, Tedeschi A . Assessment of histamine-releasing activity of sera from patients with chronic urticaria showing positive autologous skin test on human basophils and mast cells. Clin Exp Allergy 2004; 34:

1111-4.

22.Caproni M, Volpi W, Giomi B, et al. Chronic idiopathic and chronic autoimmune urticaria: clinical and immunopathologi- cal features of 68 subjects. Acta Derm Venereol 2004; 84: 288- 90.

23.Toubi E, Kessel A, Avshovich N, et al. Clinical and laboratory parameters in predicting chronic urticaria duration: a prospec- tive study of 139 patients. Allergy 2004; 59: 869-73.

24.Rose NR, Bona C. Defining criteria for autoimmune diseases ( Witebsky's postulates revisited). Immunol Today 1993; 14:

426-30.

25. G rattan CEH , Francis DM. A utoimmune urticar ia . A dv Dermatol 1999; 15: 311-40.

26.Grattan CEH, Francis DM, Slater NGP, et al. Plasmapheresis for severe, unremitting, chronic urticaria. Lancet 1992; 339:

1078-80.

27.O'Donnell BF, Barr RM, Kobza Black A, et al. Intravenous im- munoglobulin in autoimmune chronic urticaria. Br J Dermatol 1998; 138: 101-6.

28.O'Donnell BF, O'Neill CM, Francis DM, et al. Human leuco- cyte antigen class II associations in chronic idiopathic urticaria.

Br J Dermatol 1999; 140: 853-8.

29.Leznoff A, Josse RG, Denburg J, Dolovich J. Association of chronic urticaria and angioedema with thyroid autoimmunity.

Arch Dermatol 1983; 119: 636-40.

30.Turktas I, Gokcora N, Demirsoy S, Cakir N, Onal E. The asso- ciation of chronic urticaria and angioedema with autoimmune thyroiditis. Int J Dermatol 1997; 36: 187-90.

31.Gaig P, Garcia-Ortega P, Enrique E, Richart C. Successful treat- ment of chronic idiopathic urticaria associated with thyroid au- toimmunity. J Investig Allergol Clin Immunol 2000; 10: 342-5.

32.Zauli D, Deleonardi G, Foderaro S, et al. Thyroid autoimmuni- ty in chronic urticaria. Allergy Asthma Proc 2001; 22: 93-5.

33.Asero R, Lorini M, Tedeschi A. Association of chronic urticaria

with thyroid autoimmunity and Raynaud phenomenon with an-

ticentromere antibodies. J A llergy Clin Immunol 2003; 111 :

1129-30.

(8)

3 4 . Verneuil L, L econte C, Ballet JJ, et al. Association betw een chronic urticaria and thyroid autoimmunity: a prospective study involving 99 patients. Dermatology 2004; 208: 98-103.

35.Toubi E, Kessel A, Avshovich N, et al. Clinical and laboratory parameters in predicting chronic urticaria duration: a prospec- tive study of 139 patients. Allergy 2004; 59: 869-73.

36.Kandeel AA, Zeid M, Helm T, Lillie MA, Donahue E, Ambrus JL Jr. Evaluation of chronic urticaria in patients with Hashimoto thyroiditis. J Clin Immunol 2001; 21: 335-47.

37.Lanigan SW, Short P, Moult P. The association of chronic ur- ticaria and thyroid autoimmunity. Clin Exp Dermatol 1987; 12:

335-8.

38.Kikuchi Y, Fann T, Kaplan AP. Antithyroid antibodies in chron- ic urticaria and angioedema. J Allergy Clin Immunol 2003; 112:

218. 39.Fusari A, Colangelo C, Bonifazi F, Antonicelli L. The autolo- gous serum skin test in the follow-up of patients with chronic urticaria. Allergy 2005; 60: 256-8.

40.Rumbyrt JS, Katz JL, Schocket AL. Resolution of chronic ur- ticaria in patients with thyroid autoimmunity. J Allergy Clin Immunol 1995; 96: 901-5.

4 1 . Aversano M, Caiazzo P, Iorio G, Ponticiello L , L agana B, Leccese F. Improvement of chronic idiopathic urticaria with L- thyroxine: a new TSH role in immune response? Allergy 2005;

60: 489-93.

42.Kozel MM, Mekkes JR, Bossuyt PM, Bos JD. Natural course of physical and chronic urticaria and angioedema in 220 patients.

J Am Acad Dermatol 2001; 45: 387-91.

43.Cribier B. Urticaria and hepatitis. Clin Rev Allergy Immunol 2006; 30: 25-9.

44.Scully LJ, Ryan AE. Urticaria and acute hepatitis A virus in- fection. Am J Gastroenterol 1993; 88: 277-8.

45.Vaida GA, Goldman MA, Bloch KJ. Testing for hepatitis B virus in patients with chronic urticaria and angioedema. J Allergy Clin Immunol 1983; 72: 193-8.

46.Doutre MS, Beylot C, Beylot J, Bioulac P. Virus B markers in patients with chronic urticaria. 100 cases. Presse Med 1987; 16:

1009-10.

47.Reichel M, Mauro TM. Urticaria and hepatitis C. Lancet 1990;

336: 822-3.

48.Raychaudhuri SP, Kaplan M. Chronic urticaria and hepatitis C.

Int J Dermatol 1995; 34: 823-4.

49.Kanazawa K, Yaoita H, Tsuda F, Okamoto H. Hepatitis C virus infection in patients with urticaria. J Am Acad Dermatol 1996;

35: 195-8.

50.Smith R, Caul EO. Urticaria and hepatitis C. Br J Dermatol 1997;

136: 980.

51.Zauli D, Deleonardi G, Borlotti R, et al. Chronic urticaria. Arch Dermatol 2001; 137: 504-5.

52.Cribier BJ, Santinelli F, Schmitt C, et al. Chronic urticaria is not significantly associated with hepatitis C or hepatitis G infection:

a case-control study. Arch Dermatol 1999; 135: 1335-9.

53.Llanos F, Raison-Peyron N, Meunier L, et al. Hepatitis C virus

infection in patients with urticaria. J Am Acad Dermatol 1998;

38: 646.

54.Doutre MS, Beylot BM, Beylot C. Urticaria and hepatitis C in- fection. Br J Dermatol 1997; 138: 194-5.

55.Wedi B, Wagner S, Werfel T, Manns MP, Kapp A. Prevalence of Helicobacter pylori-associated gastritis in chronic urticaria.

Int Arch Allergy Immunol 1998; 116: 288-94.

56.Di Campli C, Gasbarrini A, Nucera E, et al. Beneficial effects of Helicobacter pylori eradication on idiopathic chronic ur- ticaria. Dig Dis Sci 1998; 43: 1226-9.

57.Schnyder B, Helbling A, Pichler WJ. Chronic idiopathic ur- ticaria: natural course and association with Helicobacter pylori infection. Int Arch Allergy Immunol 1999; 119: 60-3.

58.Erel F, Sener O, Erdil A, et al. Impact of Helicobacter pylori and Giardia lamblia infections on chronic urticaria. J Investig Allergol Clin Immunol 2000; 10: 94-7.

59.Federman DG, Kirsner RS, Moriarty JP, Concato J. The effect of antibiotic therapy for patients infected with Helicobacter py- lori who have chronic urticaria. J Am Acad Dermatol 2003; 49:

861-4.

60.Kozel MM, Sabroe RA. Chronic urticaria: aetiology, manage- ment and current and future treatment options. Drugs 2004; 64:

2515-36.

61.Robertson L, Greaves MW. Responses of human skin blood ves- sels to synthetic histamine analogues. Br J Clin Pharmacol 1978;

5: 319-22.

62.Erbagci Z. The leukotriene receptor antagonist montelukast in the treatment of chronic idiopathic urticaria: a single-blind, placebo-controlled, crossover clinical study. J Allergy Clin Immunol 2002; 110: 484-8.

63.Di Lorenzo G, Pacor ML, Mansueto P, et al. Randomized place- bo-controlled trial comparing desloratadine and montelukast in monotherapy and desloratadine plus montelukast in combined therapy for chronic idiopathic urticaria. J Allergy Clin Immunol 2004; 114: 619-25.

64.Bagenstose SE, Levin L, Bernstein JA. The addition of zafir- lukast to cetirizine improves the treatment of chronic urticaria in patients with positive autologous serum skin test results. J Allergy Clin Immunol 2004; 113: 134-40.

65.Reimers A, Pichler C, Helbling A, Pichler WJ, Yaw alkar N.

Zafirlukast has no beneficial effects in the treatment of chronic urticaria. Clin Exp Allergy 2002; 32: 1763-8.

66.Kaplan AP. Clinical practice. Chronic urticaria and angioedema.

N Engl J Med 2002; 346: 175-9.

67.Grattan CE, O'Donnell BF, Francis DM, et al. Randomized dou- ble-blind study of cyclosporin in chronic "idiopathic" urticaria.

Br J Dermatol 2000; 143: 365-72.

68.Toubi E, Blant A, Kessel A, Golan TD. Low-dose cyclosporin A in the treatment of severe chronic idiopathic urticaria. Allergy 1997; 52: 312-6.

69.Kessel A, Bamberger E, Toubi E. Tacrolimus in the treatment of

severe chronic idiopathic urticaria: an open-label prospective s-

tudy. J Am Acad Dermatol 2005; 52: 145-8.

(9)

70.Gach JE, Sabroe RA, Greaves MW, et al. Methotrexate-respon- sive chronic idiopathic urticaria: a report of two cases. Br J Dermatol 2001; 145: 340-3.

71.Reeves GE, Boyle MJ, Bonfield J, et al. Impact of hydroxy- chloroquine therapy on chronic urticaria: chronic autoimmune urticaria study and evaluation. Intern Med J 2004; 34: 182-6.

72.Vasagar K, Vonakis BM, Gober LM, Viksman A, Gibbons SP Jr, Saini SS. Evidence of in vivo basophil activation in chronic idiopathic urticaria. Clin Exp Allergy 2006; 36: 770-6.

7 3 . Vona kis BM, Vasagar K , G ibbons SP Jr, e t a l. Basophil FcepsilonRI histamine release parallels expression of Src-ho- mology 2-containing inositol phosphatases in chronic idiopath- ic urticaria. J Allergy Clin Immunol 2007; 119: 441-8.

Chronic Idiopathic Urticaria

Chia-Tse Weng, Yi-Hsing Chen

¹

, and Ming-Fei Liu

Chronic idiopathic urticaria is recurrent itchy wheals with daily or almost daily occurrence for at least 6 weeks,

without obvious cause. Eighty to 90% of these patients have no specific external cause for their disease, which

is therefore labeled idiopathic before. It is now recognized that as many as 30-50% of patients show evi-

dence of autoantibodies directed against either the high-affinity IgE receptor or, less frequently, against IgE. The

term autoimmune urticaria is used increasingly nowadays to reflect advances in knowledge about these func-

tional autoantibodies that activate mast cells and basophils. Autologous serum skin test is a useful in vivo screen-

ing test for autoimmune urticaria, with both sensitivity and specificity about 80%. It is generally accepted that thy-

roid autoimmunity is more prevalent in patients with chronic urticaria. However, antithyroid antibodies are not a

direct causative agent in chronic urticaria. It appears more likely that antithyroid antibodies and anti-IgE receptor

antibodies are associated, but just parallel, autoimmune events. The role of infections in chronic urticaria remains

intriguing but unresolved. The prevalence of Helicobacter pylori infection in chronic urticaria is similar to that found

in the general population. However, patients with chronic urticaria may differ in their immune response to infec-

tions or may develop infection-induced autoreactivity/ autoimmunity. Remission or improvement of chronic ur-

ticaria after H. pylori eradication was shown is some studies. Non-sedating histamine receptor antagonists should

be used as first-line agents in the treatment of these patients; however, identification of patients with autoimmune

urticaria is of increasing importance because of immunotherapy. Cyclosporin, intravenous immunoglobulin or

plasmapheresis has been reported to be successful in severely affected refractory patients. ( J Intern Med Taiwan

2008; 19: 27- 35 )