Indian Journal of Dermatology
  Publication of IADVL, WB
  Official organ of AADV
Indexed with Science Citation Index (E) , Web of Science and PubMed
 
Users online: 457  
Home About  Editorial Board  Current Issue Archives Online Early Coming Soon Guidelines Subscriptions  e-Alerts    Login  
    Small font sizeDefault font sizeIncrease font size Print this page Email this page


 
Table of Contents 
E-IJD CORRESPONDENCE
Year : 2015  |  Volume : 60  |  Issue : 3  |  Page : 323
Features of antihistamine-resistant chronic urticaria and chronic urticaria during exacerbation


Department of Dermatology, Guangzhou Institute of Dermatology, Guangzhou, Guangdong, China

Date of Web Publication6-May-2015

Correspondence Address:
Zhu Huilan
Department of Dermatology, Guangzhou Institute of Dermatology, Guangzhou, Guangdong
China
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-5154.156458

Rights and Permissions



How to cite this article:
Huilan Z, Bihua L, Runxiang L, Jiayan L, Luyang L, Zhenjie L. Features of antihistamine-resistant chronic urticaria and chronic urticaria during exacerbation . Indian J Dermatol 2015;60:323

How to cite this URL:
Huilan Z, Bihua L, Runxiang L, Jiayan L, Luyang L, Zhenjie L. Features of antihistamine-resistant chronic urticaria and chronic urticaria during exacerbation . Indian J Dermatol [serial online] 2015 [cited 2019 Nov 17];60:323. Available from: http://www.e-ijd.org/text.asp?2015/60/3/323/156458


Sir,

In clinic, the treatment of chronic urticaria (CU) commonly presents some challenges for the dermatologist. Antihistamines are the first-line treatment in CU, [1] but sometimes CU is resistant to it, even high doses. In another side, urticaria is a skin disease characterized by short-lived wheals and we all know that the wheals in CU can fade by themselves. What are the differences between antihistamines-sensitive CU and antihistamines-resistant CU and what are the differences during CU exacerbation and during remission? To study these maybe good for further understanding the pathogenesis of CU.

In our study, the plasma levels of prothrombin fragment 1 + 2 (F1 + 2), tissue factor (TF), thrombomodulin (TM), high molecular weight kininogen (HMWK), tissue-type plasminogen activator (t-PA), C5a, C3, C4, antistreptolysin O (ASO), rheumatoid factors (RF), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were determined in CU patients (17 antihistamines-sensitive CU and 23 antihistamines-resistant CU; 22 during CU exacerbation and 18 during remission). Urticaria activity score and autologous serum skin test (ASST) were also assessed.

Plasma concentration of F1 + 2 in exacerbation CU patients (985.36 ± 285.77 pmol/L) were significantly higher than those in remission CU patients (579.40 ± 305.87 pmol/L) (P < 0.01). However there was no significant difference of plasma levels of TF, TM, HMWK, t-PA, C5a and serum levels of C3, C4, ASO, RF, CRP and ESR between exacerbation CU patients and remission CU patients (P > 0.05) [Figure 1] and [Figure 2]. Plasma levels of C5a were higher in antihistamines-resistant CU patients (50.67 ± 16.83 pmol/L) than those in antihistamines-sensitive CU patients (40.43 ± 10.89 pmol/L) (P < 0.05), but there was no statistical difference in plasma levels of F1 + 2, TF, TM, HMWK, t-PA and serum levels of C3, C4, ASO, RF, CRP and ESR between them (P > 0.05) [Figure 3] and [Figure 4]. In CU patients, antihistamines sensitive/antihistamines resistant was correlated with symptom scores and duration of wheals (r = 0.42, P < 0.01; r = 0.57, P < 0.01). In antihistamines-resistant CU patients, we found higher symptom scores and longer duration of wheals. However, antihistamines sensitive/antihistamines resistant was not correlated disease course (r = 0.11, P > 0.05) [Table 1]. Compared with antihistamines-sensitive CU patients, antihistamines-resistant CU patients was characterized with more positive ASST (12/23 in antihistamines-sensitive CU patients versus 15/17 in antihistamines-resistant CU patients; P < 0.05) [Table 2].
Table 1: Correlation with response to antihistamines in CU patients


Click here to view
Table 2: Results of ASST in antihistamine-resistant and antihistamine-sensitive CU patients


Click here to view
Figure 1: Plasma levels of F1 + 2, tissue factor, thrombomodulin, high molecular weight kininogen and tissue-type plasminogen activator in chronic urticaria patients during exacerbation and during remission (*P < 0.01)

Click here to view
Figure 2: Plasma levels of C5a and serum levels of C3, C4, antistreptolysin O, rheumatoid factors, C-reactive protein and erythrocyte sedimentation rate in chronic urticaria patients during exacerbation and during remission (P > 0.05)

Click here to view
Figure 3: Plasma levels of C5a and serum levels of C3, C4, antistreptolysin O, rheumatoid factors, C-reactive protein and erythrocyte sedimentation rate in antihistamine-resistant and antihistamine-sensitive chronic urticaria patients (*P < 0.05)

Click here to view
Figure 4: Plasma levels of F1 + 2, tissue factor, thrombomodulin, high molecular weight kininogen and tissue-type plasminogen in antihistamine-resistant and antihistamine-sensitive chronic urticaria patients (P > 0.05)

Click here to view


In this study, we found that plasma concentrations of F1 + 2 in CU patients during the exacerbation were significantly higher than those in remission patients (P < 0.01). We assume that the concentration of thrombin tends to recover as CU comes to remission gradually. This may give explanation for the phenomenon why the wheals in CU fade by themselves. In our former study, we found that antihistamine can act on coagulation as the levels of coagulant factors trend toward recovery after antihistamine administration. [2] Studies have shown that thrombin participates in mast cell degranulation by activating protein kinase receptor on the mast cell surface. [3] Solute permeability may result in cutis and mucosal edema. [4] But this effect can be blocked by antihistamine drug administration or mast cell granule attenuation. [5] Antihistamine may play a key role in inhibiting the activation of coagulation cascade in CU.

We also observed that complement C5a concentration increased significantly in antihistamine-resistant patients. The resistance to antihistamine may be related to upregulation of plasma levels of C5a in CU patients. It has been demonstrated a new complement activation pathway that C5a generated in the absence of C3 by thrombin, which took place of C5 convertase in the classical pathway. [6] Pathogenic IgG cross-links the IgE receptor directly to cause histamine release, and the activation is augmented by complement. C5a is the complement agonist that is responsible for the augmented histamine release. [7] We also found the antihistamines-resistant CU patients with upregulation of plasma levels of C5a, higher activity scores, longer duration of wheals and more positive ASST. hence we considered that resistance to antihistamine in CU patients may be related to immunoreaction intervened by complement.


   Conclusion Top


The resistance to antihistamine could be related to upregulation of plasma levels of C5a, higher activity scores, longer duration of wheals and more positive ASST, but not to those of coagulant and anticoagulant factors and fibrinolytic markers in CU patients; CU during the exacerbation and during remission maybe differ in coagulation.

 
   References Top

1.
Zuberbier T, Asero R, Bindslev-Jensen C, Walter Canonica G, Church MK, Giménez-Arnau AM, et al. EAACI/GA (2) LEN/EDF/WAO guideline: Management of urticaria. Allergy 2009;64:1427-43.  Back to cited text no. 1
    
2.
Zhu H, Liang B, Li R, Li J, Lin L, Ma S, et al. Activation of coagulation, anti-coagulation, fibrinolysis and the complement system in patients with urticaria. Asian Pac J Allergy Immunol 2013;31:43-50.  Back to cited text no. 2
    
3.
Kido H, Fukusen N, Katunuma N, Morita T, Iwanaga S. Tryptase from rat mast cells converts bovine prothrombin to thrombin. Biochem Biophys Res Commun 1985;132:613-9.  Back to cited text no. 3
[PUBMED]    
4.
Schaeffer RC Jr, Gong F, Bitrick MS Jr, Smith TL. Thrombin and bradykinin initiate discrete endothelial solute permeability mechanisms. Am J Physiol 1993;264:H1798-809.  Back to cited text no. 4
    
5.
Cirino G, Cicala C, Bucci MR, Sorrentino L, Maraganore JM, Stone SR. Thrombin functions as an inflammatory mediator through activation of its receptor. J Exp Med 1996;183:821-7.  Back to cited text no. 5
    
6.
Huber-Lang M, Sarma JV, Zetoune FS, Rittirsch D, Neff TA, McGuire SR, et al. Generation of C5a in the absence of C3: A new complement activation pathway. Nat Med 2006;12:682-7.  Back to cited text no. 6
    
7.
Kikuchi Y, Kaplan AP. A role for C5a in augmenting IgG-dependent histamine release from basophils in chronic urticaria. J Allergy Clin Immunol 2002;109:114-8.  Back to cited text no. 7
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1], [Table 2]



 

Top
Print this article  Email this article
 
 
  Search
 
  
    Similar in PUBMED
    Article in PDF (396 KB)
    Citation Manager
    Access Statistics
    Reader Comments
    Email Alert *
    Add to My List *
* Registration required (free)  


   Conclusion
    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed1874    
    Printed18    
    Emailed2    
    PDF Downloaded55    
    Comments [Add]    

Recommend this journal