今日の臨床サポート

じんま疹

著者: 高萩俊輔1) 広島大学 大学院医系科学研究科 皮膚科学

著者: 秀 道広2) 広島市民病院病院長/広島大学病院特別顧問・客員教授

監修: 戸倉新樹 掛川市・袋井市病院企業団立 中東遠総合医療センター 参与/浜松医科大学 名誉教授

著者校正/監修レビュー済:2021/07/07
参考ガイドライン:
  1. 秀 道広ら:日本皮膚科学会ガイドライン 蕁麻疹診療ガイドライン2018. 日本皮膚科学会雑誌 128: 2503-624, 2018.
  1. Zuberbier T. et al. The Eaaci/Ga2Len/Edf/Wao Guideline for the Definition, Classification, Diagnosis and Management of Urticaria. Allergy 73: 1393-414, 2018.
患者向け説明資料

概要・推奨   

疾患の概要:
  1. じんま疹とは、膨疹、すなわち紅斑を伴う一過性、限局性の浮腫が病的に出没する疾患であり、多くは痒みを伴う。眼瞼や口唇などの皮膚ないし粘膜の深部を中心とした限局性浮腫のことを特に血管性浮腫と呼ぶ。血管性浮腫は、それ単独で、あるいはじんま疹に合併して出現する。
  1. 特発性のじんま疹と刺激誘発型のじんま疹に大きく分類される。
  1. 特発性のじんま疹は、最も多いじんま疹の病型で、特定の誘因なく毎日規則的に皮疹の出没を繰り返す。刺激誘発型のじんま疹は、特定の刺激や条件が加わったときに皮疹が誘発される。
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
高萩俊輔 : 特に申告事項無し[2021年]
秀 道広 : 講演料(サノフィ,田辺三菱製薬,大鵬薬品工業,ノバルティスファーマ),研究費・助成金など(グラクソ・スミスクライン),奨学(奨励)寄付など(田辺三菱製薬,大鵬薬品工業)[2021年]
監修:戸倉新樹 : 講演料(田辺三菱,サノフィ,マルホ,協和キリン),研究費・助成金など(ノバルティス,レオファーマ)[2021年]

改訂のポイント:
  1. 定期レビューを行った(軽微な変更のみ)。

病態・疫学・診察

疾患情報  
  1. じんま疹は膨疹、すなわち紅斑を伴う一過性、限局性の浮腫が病的に出没する疾患であり、多くは痒みを伴う。通常のじんま疹に合併して、あるいは単独に、皮膚ないし粘膜の深部を中心とした限局性浮腫のことを特に血管性浮腫と呼ぶ。
  1. じんま疹の特徴は個々の皮疹の一過性にあるため、痒みを伴う紅斑が24時間以内に出没することが確認できれば、ほぼじんま疹と考えてよい。
  1. じんま疹の病型は、特発性のじんま疹と刺激誘発型のじんま疹に大きく分類される。特発性のじんま疹は、特定の誘因なく、毎日規則的に皮疹の出没を繰り返すタイプで、病悩期間により急性蕁麻疹と慢性蕁麻疹に分けられる。刺激誘発型のじんま疹は、特定の刺激や条件が加わったときに皮疹が誘発されるタイプで、誘発刺激の種類により種々のじんま疹病型を含む。
  1. 患者のみならず医療従事者が想定しているのは外来抗原によるアレルギー性のじんま疹であるが、実際には特発性のじんま疹が最も多く、原因として特定の抗原を同定できることは少ない。田中らによる広島大学病院皮膚科外来での集計ではアレルギー性のじんま疹の割合は全じんま疹中5.4%であった[1]。そのため、アレルギー性のじんま疹が疑われる場合を除き、すべてのじんま疹に網羅的にI型アレルギーの検査を行うことは推奨されない。
 
じんま疹の主な病型:
特発性のじんま疹:
  1. 急性蕁麻疹(発症後6週間以内)
  1. 慢性蕁麻疹(発症後6週間以上)
刺激誘発型のじんま疹:
  1. アレルギー性のじんま疹
  1. 食物依存性運動誘発アナフィラキシー
  1. 非アレルギー性のじんま疹
  1. アスピリン蕁麻疹(不耐症によるじんま疹)
  1. 物理性蕁麻疹(機械性蕁麻疹、寒冷蕁麻疹、日光蕁麻疹、温熱蕁麻疹、遅延性圧蕁麻疹、水蕁麻疹)
  1. コリン性蕁麻疹
  1. 接触蕁麻疹
血管性浮腫:
  1. 特発性の血管性浮腫
  1. 刺激誘発型の血管性浮腫(振動血管性浮腫を含む)
  1. ブラジキニン起因性の血管性浮腫
  1. 遺伝性血管性浮腫
じんま疹関連疾患:
  1. 蕁麻疹様血管炎
  1. 色素性蕁麻疹
  1. Schnitzler症候群およびクリオピリン関連周期熱症候群
問診・診察のポイント  
  1. 痒みを伴う紅斑が出現した後、24時間以内に色素沈着を残さず消退することを確認する。受診時に皮疹がみられないこともしばしばある。

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文献 

著者: David M Lang
雑誌名: Allergy Asthma Proc. 2014 Jan-Feb;35(1):10-6. doi: 10.2500/aap.2014.35.3722.
Abstract/Text Chronic urticaria/angioedema (CUA) continues to be a vexing condition for both patients and health care providers. Despite progress made in recent years to improve our understanding of the pathogenesis of CUA and its treatment, many patients continue to experience ongoing symptoms and impaired quality of life. In the overwhelming majority of cases, a definite etiology is not identified. Laboratory testing may be justified based on its "reassurance value"; however, extensive routine testing is not favorable from a cost-benefit standpoint and does not lead to improved patient care outcomes. The target for effective management is to control CUA with a combination of avoidance measures, lifestyle changes, and regular administration of medication. A step-care approach to pharmacologic management that is favorable from the standpoint of balancing the potential for benefit with the potential for harm can lead to substantial improvement in quality of life. This article will focus on achieving improved outcomes for patients with CUA based on evidence-directed recommendations for diagnosis and management.

PMID 24433592  Allergy Asthma Proc. 2014 Jan-Feb;35(1):10-6. doi: 10.2・・・
著者: Rafael Rabelo-Filardi, Renato Daltro-Oliveira, Régis A Campos
雑誌名: Int Arch Allergy Immunol. 2013;161(3):197-204. doi: 10.1159/000346896. Epub 2013 Mar 15.
Abstract/Text BACKGROUND: Although some authors have already evaluated the predictive value of various parameters regarding the duration of chronic spontaneous urticaria (CSU), it remains uncertain which ones have importance in clinical practice as prognostic factors that indeed enable prediction. Similarly, some authors have investigated parameters that might be related to severe cases of CSU. However, the results of studies evaluating several parameters as markers of disease severity are fragmented. Thus, we performed a systematic review to summarize the findings of studies investigating the parameters associated with CSU duration and severity.
METHODS: Two authors independently searched PubMed until June 2012 for observational retrospective or prospective studies addressing clinical or laboratory parameters associated with disease duration or severity in CSU patients.
RESULTS: We found 1,136 potentially relevant published papers related to the subject, 34 of which were included in the systematic review. A total of 16, 6 and 12 articles evaluated CSU parameters on severity, duration or both, respectively.
CONCLUSIONS: Our findings suggest that disease severity might predict CSU duration. Similarly, evidence suggests that plasma levels of prothrombin fragment 1 + 2, D-dimer and C-reactive protein may function as markers of CSU severity.

Copyright © 2013 S. Karger AG, Basel.
PMID 23548885  Int Arch Allergy Immunol. 2013;161(3):197-204. doi: 10.・・・
著者: Carlo Caffarelli, Barbara Cuomo, Fabio Cardinale, Salvatore Barberi, Carlotta Povesi Dascola, Fabio Agostinis, Fabrizio Franceschini, Roberto Bernardini
雑誌名: Acta Derm Venereol. 2013 May;93(3):268-72. doi: 10.2340/00015555-1511.
Abstract/Text Chronic urticaria is a distressing condition with high costs. The aim of this literature review was to assess the relative frequency of causes of chronic urticaria in childhood and to provide guidance on which laboratory tests should be performed. Using PubMed, EMBASE and Cochrane databases, the literature from 1966 to 2010 (week 25) was systematically reviewed. Data from studies conducted on children who had had urticaria for at least 6 weeks, and assessing at least 3 different causes of urticaria, were analysed by reviewers using independent extraction. Six studies, all of low quality, met the inclusion criteria. Idiopathic and physical urticaria were common. Infections, autoimmunity and allergy were also reported. We conclude that children with chronic urticaria not caused by physical stimuli should undergo tests for allergy or infections only when there is a history of cause-effect correlation. High-quality trials are warranted to evaluate the causes of chronic urticaria in childhood.

PMID 23224228  Acta Derm Venereol. 2013 May;93(3):268-72. doi: 10.2340・・・
著者: Lindsey A Brodell, Lisa A Beck
雑誌名: Ann Allergy Asthma Immunol. 2008 Mar;100(3):181-8; quiz 188-90, 215. doi: 10.1016/S1081-1206(10)60438-3.
Abstract/Text OBJECTIVES: To review diseases that can present with cutaneous signs and symptoms that mimic those observed in chronic urticaria and to discuss the workup necessary to distinguish these diseases from chronic urticaria.
DATA SOURCES: We performed a PubMed search using the following keywords: urticaria, cryopyrin, Sweet syndrome, subacute cutaneous lupus, urticarial vasculitis, urticaria pigmentosa, angioedema, fixed drug eruption, bullous pemphigoid, and reticular erythematous mucinosis. Appropriate chapters in general dermatology textbooks were also reviewed.
STUDY SELECTION: Articles that related to disease states, which present with persistent urticarial lesions, were catalogued for use in this review.
RESULTS: Besides acute, chronic, and physical urticarias, there are 2 categories of diseases that have urticarial lesions. The first group includes those in which the skin lesions are almost indistinguishable from those seen in patients with chronic idiopathic urticaria. Thus, the diagnosis relies on a careful history and physical examination, and in some cases laboratory studies are required. The second group are ones that have skin lesions that at one point in their development have an urticaria-like appearance or on rare occasion may have such lesions. These latter diseases are numerous, and we have tried to highlight the ones that most mimic chronic idiopathic urticaria or are more common.
CONCLUSIONS: A working knowledge of the diseases that can present with urticarial lesions is essential to accurately diagnose and effectively treat these symptomatic and sometimes serious conditions.

PMID 18426134  Ann Allergy Asthma Immunol. 2008 Mar;100(3):181-8; quiz・・・
著者: Martina M A Kozel, Patrick M M Bossuyt, Jan R Mekkes, Jan D Bos
雑誌名: J Am Acad Dermatol. 2003 Mar;48(3):409-16. doi: 10.1067/mjd.2003.142.
Abstract/Text BACKGROUND: The value of laboratory tests in chronic urticaria is still controversial.
OBJECTIVE: Our aim was to assess this value in clinical studies, and to identify factors explaining the variation in the number of identified causes.
METHODS: A total of 4 electronic databases were searched, and a manual literature search was performed. Only unselected patient series with more than 50 adult patients were included. From each included study predefined items were recorded to assess their quality (consecutive patients, use of standardized diagnostic criteria) and validity (follow-up, assessment of treatment effects, level of evidence).
RESULTS: A total of 29 studies were included, involving 6462 patients. The verification of the validity of the results and the level of evidence of the included studies were limited.
CONCLUSION: No relationship between the number of identified diagnoses and the number of performed laboratory tests, the different settings, the study design, or the publication period was found. On the basis of this systematic review and the relevant literature, a clinical guideline in the form of a flowchart is presented.

PMID 12637921  J Am Acad Dermatol. 2003 Mar;48(3):409-16. doi: 10.1067・・・
著者:
雑誌名: Clin Exp Allergy. 1995 Jul;25(7):586-95.
Abstract/Text Allergic diseases affect at least 15% of the population and are the cause of much ill-health. 'Clinical immunology and allergy', the term used by the Department of Health in England and Wales for this area of specialization, is recognized as a separate specialty of medicine under the National Health Service. Many organ-based hospital consultants (e.g. chest physicians) have allergy as a special interest or subspecialty. Allergists deal largely with 'itch, sneeze, cough and wheeze' and so are experts in: summer hay fever (seasonal, allergic, conjunctivorhinitis); perennial rhinitis (symptoms of a 'permanent cold'); allergic asthma (including occupational asthma); allergy to stinging insects (especially wasps and bees); allergy to drugs; allergy-related skin disorders, i.e. urticaria, angioedema, atopic eczema and contact dermatitis; food allergy and food intolerance; anaphylaxis (acute generalized allergic reaction); evaluating the role of allergy in non-specific/polysymptomatic illness. Children with allergic disease should be under the overall care of a paediatrician since the progression of allergies in children differs from that in adults. Good allergy practice involves teamwork by doctors, nurses and dietitians. The investigation of allergy patients includes skin tests and challenge procedures (e.g. food allergy tests) as well as various specialized laboratory investigations. Good clinical practice by providers and the effective use of allergy services by purchasers should improve prognosis and cut costs of treatment in allergic disease.

PMID 8521176  Clin Exp Allergy. 1995 Jul;25(7):586-95.
著者: Bettina Wedi, Ulrike Raap, Dorothea Wieczorek, Alexander Kapp
雑誌名: Allergy Asthma Clin Immunol. 2009 Dec 1;5(1):10. doi: 10.1186/1710-1492-5-10. Epub 2009 Dec 1.
Abstract/Text Urticaria is a group of diseases that share a distinct skin reaction pattern. Triggering of urticaria by infections has been discussed for many years but the exact role and pathogenesis of mast cell activation by infectious processes is unclear. In spontaneous acute urticaria there is no doubt for a causal relationship to infections and all chronic urticaria must have started as acute. Whereas in physical or distinct urticaria subtypes the evidence for infections is sparse, remission of annoying spontaneous chronic urticaria has been reported after successful treatment of persistent infections. Current summarizing available studies that evaluated the course of the chronic urticaria after proven Helicobacter eradication demonstrate a statistically significant benefit compared to untreated patients or Helicobacter-negative controls without urticaria (p < 0.001). Since infections can be easily treated some diagnostic procedures should be included in the routine work-up, especially the search for Helicobacter pylori. This review will update the reader regarding the role of infections in different urticaria subtypes.

PMID 20066173  Allergy Asthma Clin Immunol. 2009 Dec 1;5(1):10. doi: 1・・・
著者: Cansin Sackesen, Bulent E Sekerel, Fazil Orhan, Can Naci Kocabas, Ayfer Tuncer, Gonul Adalioglu
雑誌名: Pediatr Dermatol. 2004 Mar-Apr;21(2):102-8. doi: 10.1111/j.0736-8046.2004.21202.x.
Abstract/Text Urticaria is a common disease in children. In contrast to the ease of its diagnosis, etiologic factors are often difficult to determine. In order to study whether differences exist among various forms of urticaria in childhood and whether the patterns of different types of urticaria differ between adults and children, we extensively studied the possible causes of urticaria in children. Fifty-four children (23 girls and 31 boys; ages 1-19 years) with various forms of urticaria were included in the study. In all cases, questions about food allergies, food additive intolerance, drug intake, signs of infection, causes of physical urticaria, insect bites, and personal and family history of atopy were asked. Clinical characteristics of the disease, such as duration, recurrence, and associated angioedema and symptoms of anaphylaxis were also investigated. Detailed laboratory tests, including serologic, autoimmune, and allergic analyses, were conducted to reveal the probable etiologies of urticaria. Of the study patients, 68.5% and 31.5% were diagnosed as having acute and chronic urticaria, respectively. The patient group with chronic urticaria was older and included more boys than the acute group. In the acute urticaria group, infection was the most frequently documented cause (48.6%), followed by drugs (5.4%), and food allergies (2.7%), whereas in chronic urticaria, physical factors were the leading cause (52.94%). The most frequently documented infection was urinary tract infection, followed by serologically determined infections of Chlamydia pneumoniae and Helicobacter pylori. In this study we found indications that infections were frequently associated with urticaria, which suggests that urticaria management should include a survey of certain infectious agents in addition to a detailed history.

PMID 15078346  Pediatr Dermatol. 2004 Mar-Apr;21(2):102-8. doi: 10.111・・・
著者: M Sakurai, M Oba, K Matsumoto, Y Tokura, F Furukawa, M Takigawa
雑誌名: J Dermatol. 2000 Feb;27(2):87-93.
Abstract/Text We treated 19 Japanese patients with acute urticaria presumably caused by infection during the five years from 1994 to 1998. The patients' ages ranged from 2 to 66 years (8 males and 11 females). Most of them had urticaria, angioedema, high fever, neutrophilia, and high serum levels of C reactive protein (CRP). The skin rash lasted more than 24 hours. In four patients, a flow cytometric analysis revealed that the percentage of circulating T cells bearing T-cell receptor V beta 3 was decreased during the active stage and that this decrease was sustained for at least 2 to 3 weeks. This suggests that certain T-cell populations were numerically altered in association with the occurrence of the disease. A retrospective review indicated that the combination therapy with corticosteroid and antibiotics was more effective than the single use of either agent.

PMID 10721655  J Dermatol. 2000 Feb;27(2):87-93.
著者: M D Del Pozo, M Audícana, J M Diez, D Munoz, I J Ansotegui, E Fernández, M García, M Etxenagusia, I Moneo, L Fernández de Corres
雑誌名: Allergy. 1997 May;52(5):576-9.
Abstract/Text Anisakis simplex, a parasite of fish and cephalopods, can induce IgE-mediated reactions. This study aimed to determine the etiologic role of A. simplex in patients affected by urticaria/angioedema (AE) or anaphylaxis. We studied 100 adult subjects suffering acute episodes of urticaria/AE, by anamnesis, prick tests with A. simplex and fish-mix extracts, and total and specific IgE to both A. simplex and cod. The following criteria of A. simplex allergy were considered: 1) urticaria/AE within 6 h after fish ingestion; 2) specific IgE to A. simplex; 3) positive prick test to A. simplex extract; 4) exclusion of other suspected causes. Double-blind, placebo-controlled food challenge was not carried out because ethical considerations forbid challenge with a parasite. Specific IgE to A. simplex (> 0.7 kU/l) was found in 22 subjects, but only eight were diagnosed as having A. simplex allergy. Other allergens were involved in 37 patients, and 55 cases were considered idiopathic. Specific IgE to fish (> 0.7 kU/l) was found in two patients, but only one was diagnosed as having fish allergy. We concluded that A. simplex is an important etiologic factor in acute urticaria. We suggest that it should be considered in cases of urticaria/AE or anaphylaxis, especially after fish ingestion.

PMID 9201371  Allergy. 1997 May;52(5):576-9.
著者: Alvaro Daschner, Consolación De Frutos, Ana Valls, Francisco Vega
雑誌名: Arch Dermatol Res. 2010 Oct;302(8):625-9. doi: 10.1007/s00403-010-1069-9. Epub 2010 Jul 14.
Abstract/Text Acute urticaria is defined as evanescent wheals with a duration period of up to 6 weeks. Yet within acute urticaria, IgE-mediated urticaria lasts rarely more than 48 h, whereas longer duration periods are frequently unfruitful with respect to diagnostic work-up. We hypothesize the differences in immunologic features in immediate type urticaria versus prolonged acute urticaria within the model of Anisakis simplex (A. simplex) sensitization-associated urticaria. We included 57 patients with gastro-allergic Anisakiasis (GAA) and urticaria duration of less than 48 h and 17 patients with A. simplex sensitization-associated prolonged acute urticaria (PROL), defined as urticaria duration between 3 days and 6 weeks. As control group served 23 patients with A. simplex sensitization-associated chronic urticaria (CU+). We compared total IgE as well as specific IgE, IgG and IgG(4) against A. simplex. Median total IgE was higher in GAA than in PROL or CU+ [442 (interquartile range, IQR 198-995) vs. 117 (68-261) or 251 (94-382) kU/l, respectively]. Median-specific IgE was higher in GAA than in PROL or CU+ [62 (IQR 24.1-99) vs. 12.3 (6-30.9) or 14.2 (6.2-44.9) kU/l, respectively]. The differences were statistically significant at P < 0.001 for GAA against PROL and at P < 0.003 for GAA against CU+. Also, specific IgG and IgG(4) levels were higher in GAA than in PROL or CU+ at the same significance level. The levels of total IgE or specific immunoglobulin isotypes were not significantly different between PROL and CU+. In the model of A. simplex sensitization-associated urticaria, immediate-type urticaria in GAA is immunologically different from prolonged acute urticaria, which, in turn, shows features nearer to chronic urticaria than to gastro-allergic Anisakiasis. Thus, in an allergological evaluation of urticaria, we propose a possible benefit of a distinction of the duration period at 48 h, and not 6 weeks, when differentiating acute versus chronic urticaria.

PMID 20628748  Arch Dermatol Res. 2010 Oct;302(8):625-9. doi: 10.1007/・・・
著者: K Kanazawa, H Yaoita, F Tsuda, H Okamoto
雑誌名: J Am Acad Dermatol. 1996 Aug;35(2 Pt 1):195-8.
Abstract/Text BACKGROUND: Hepatitis C virus (HCV) infection induces variable skin manifestations.
OBJECTIVE: Our purpose was to determine whether there is an association between HCV infection and urticaria.
METHODS: Antibody to HCV (anti-HCV) and HCV genotypes were determined in patients with urticaria and in a control population.
RESULTS: Anti-HCV was detected in 19 (24%) of 79 patients with urticaria, and HCV RNA was detected in 17 (22%). Genotypes of HCV were II/1b in 12 (71%), III/2a in 4 (24%), and IV/2b in 1 (6%). The 17 patients with HCV RNA were older (53 +/- 14 vs 41 +/- 14 years, p < 0.01), and their eruption lasted longer (35% vs 6%, p < 0.05) and left pigmentation more frequently (53% vs 3%, p < 0.001). They had higher levels of alanine aminotransferase (67 +/- 34 vs 25 +/- 17 U/L, p < 0.001), aspartate aminotransferase (51 +/- 23 vs 21 +/- 8 U/L, p < 0.001), zinc turbidity test (12.8 +/- 3.1 vs 9.3 +/- 3.7 Kunkel units, p < 0.001), and IgG (1919 +/- 320 vs 1622 +/- 349 mg/100 ml, p < 0.01) than the patients without HCV RNA.
CONCLUSION: HCV could be a significant cause of urticaria. Chronic urticaria associated with HCV infection has peculiar clinical, serologic, and biochemical characteristics that could make it a distinct clinical entity with an indication for interferon therapy.

PMID 8708019  J Am Acad Dermatol. 1996 Aug;35(2 Pt 1):195-8.
著者: B J Cribier, F Santinelli, C Schmitt, F Stoll-Keller, E Grosshans
雑誌名: Arch Dermatol. 1999 Nov;135(11):1335-9.
Abstract/Text OBJECTIVE: To study the prevalence of hepatitis C virus (HCV) and hepatitis G virus (HGV) infection in patients with chronic urticaria.
DESIGN: Prospective case-control study and literature review.
SETTING: Dermatology department of an academic medical center in Strasbourg, France.
PATIENTS: One hundred ten consecutive patients with typical urticaria lasting longer than 2 months were seen between March 1, 1997, and August 31, 1998. None had a history of viral hepatitis. Age- and sex-matched patients (n = 110) seen in the same department and during the same period were included for controls. None of the controls had a history of urticaria, pruritic dermatosis, or hepatitis.
MAIN OUTCOME MEASURES: The detection of HCV antibodies through a third-generation enzyme-linked immunosorbent assay. To detect early HCV infection without plasmatic antibodies, genomic amplification of HCV RNA was carried out in all patients using 2 different methods. Hepatitis G virus RNA was detected only by genomic amplification. All measures were planned before data collection.
RESULTS: Antibodies to HCV were found in 1 patient with urticaria and in 1 of the control group (0.9% of each group). None had circulating HCV RNA, and liver function test results were within the reference range. Genomic amplification without HCV antibodies was not observed. Two patients with urticaria and 2 of the control group (1.8% of each group) had circulating HGV RNA, but they had neither coinfection with HCV nor changes in their liver function test results.
CONCLUSIONS: Systematic HCV screening in patients with chronic urticaria is not cost-effective, at least in Europe, because hepatitis C rates were similar to those of the general population. We could not confirm the hypothesis that urticaria occurs in an early phase of HCV infection-ie, before evidence of HCV can be detected by serologic testing. Hepatitis C virus is unlikely to be the cause of urticaria in the infected patient detected in this study because of the absence of HCV RNA and changes on liver function tests. Hepatitis G virus is also unlikely to be a cause of urticaria, as the rate of HGV positivity in this study was even lower than that in the general French population.

PMID 10566831  Arch Dermatol. 1999 Nov;135(11):1335-9.
著者: M M Kozel, J R Mekkes, P M Bossuyt, J D Bos
雑誌名: Arch Dermatol. 1998 Dec;134(12):1575-80.
Abstract/Text OBJECTIVE: To assess the value of extensive laboratory screening for the identification of causes in patients with chronic urticaria and/or angioedema.
DESIGN: In a prospective study involving 220 patients, 2 diagnostic strategies were compared: the combination of detailed history taking and limited laboratory investigations vs detailed history taking and extensive laboratory screening. The results of the extensive screening program were initially kept secret from the patients and the physicians. Later, all results were disclosed, and an investigation was undertaken to find out whether this information changed the initial diagnosis. The patients were followed up for 1 year to evaluate the results of interventions and to detect latent causes.
SETTING: The study was performed in the outpatient department of a secondary and tertiary care center with institutional practice.
PATIENTS: A total of 238 consecutive new patients with chronic urticaria and/or angioedema edema were referred; 18 of them refused participation. One patient was unavailable for follow-up.
MAIN OUTCOME MEASURE: The difference in the number of identified causes between both approaches and the nature of the causes that would have been missed by omitting extensive laboratory screening.
RESULTS: With a questionnaire and the limited laboratory tests, a cause was found in 45.9% of the patients, compared with 52.7% with the questionnaire and the extended screening program. Except for one parasitic infection, missed diagnoses were mainly adverse reactions to drugs or food detected by standard elimination procedures, not by laboratory investigations.
CONCLUSION: Routine laboratory screening did not contribute substantially to the diagnosis of chronic urticaria or to the detection of underlying disorders.

PMID 9875196  Arch Dermatol. 1998 Dec;134(12):1575-80.
著者: Mikihisa Sakurane, Akiko Shiotani, Fukumi Furukawa
雑誌名: J Dermatol. 2002 Jan;29(1):23-7.
Abstract/Text In order to understand the pathogenic relationship between Helicobacter pylori (H. pylori) and skin diseases, we examined the serum levels of IgG antibody against H. pylori and then performed gastroscopic examinations in Japanese patients with chronic skin diseases. These H. prylori-positive patients were treated with antibacterial eradication therapy, and therapeutic efficacy was evaluated. A total of 198 patients who were resistant to conventional therapies were randomly selected. They included 50 cases with chronic urticaria, 32 with pruritus cutaneous, 74 with atopic dermatitis, 15 with nummular dermatitis, 17 with prurigo chronica multiformis, 6 with psoriasis vulgaris, and 4 with erythroderma. Positive anti-H. pylori antibody was detected in 102 out of these 198 patients; more than half of the ones with chronic urticaria, pruritus cutaneous, nummular dermatitis, and prurigo chronica multiformis had positive antibodies. Gastroscopy was then performed in 48 cases with positive antibodies. Eradication therapy was effective in 60% of the patients with chronic urticaria, in 58% with pruritus cutaneous, in 54% with nummular dermatitis, and in 50% with prurigo chronica multiformis. In chronic skin diseases, persistent infection with H. pylori may be an eruption trigger and may cause deterioration of the disease into an in tractable and chronic form.

PMID 11837570  J Dermatol. 2002 Jan;29(1):23-7.
著者: Daniel G Federman, Robert S Kirsner, John P Moriarty, John Concato
雑誌名: J Am Acad Dermatol. 2003 Nov;49(5):861-4. doi: 10.1067/S0190.
Abstract/Text BACKGROUND: Several small trails looking at antibiotic therapy targeted at Helicobacter pylori for the treatment of chronic urticaria have been published and have had conflicting results. We conducted a systematic review of existing studies to help answer the clinical question of whether this therapy has a role in the treatment of chronic urticaria.
METHODS: We identified studies published in the English language with searches of MEDLINE, PREMEDLINE, American College of Physicians Journal Club, Database of Abstracts of Reviews of Effectiveness, and Cochrane Libraries using the key words "Helicobacter pylori" and "urticaria." Relevant studies from bibliography reviews were also included. Studies included met the following criteria: (1) patients had urticaria for at least 6 weeks; (2) other known causes of urticaria were excluded by appropriate testing; (3) the initial diagnosis of H pylori infection was made by either serology, urea breath test, or upper endoscopy; and (4) an adequate trial of an antibiotic with known activity against H pylori was completed.
RESULTS: In all, 10 studies met our inclusion criteria. The rate of remission of urticaria when H pylori was eradicated was 30.9% (59/191) compared with 21.7% (18/83) when H pylori was not eradicated; the background remission rate among control subjects without H pylori infection was 13.5% (10/74). When data from the 10 studies were combined, eradication of H pylori was both quantitatively and statistically associated with remission of urticaria (odds ratio 2.9; 95% confidence interval 1.4-6.8; P =.005).
CONCLUSION: We found that resolution of urticaria was more likely when antibiotic therapy was successful in eradication of H pylori infection than when patients who were infected did not achieve eradication. These results suggest that clinicians, after considering other causes of urticaria, should constitute (1) testing for H pylori; (2) treating with appropriate antibiotics if H pylori is present; and (3) confirming successful eradication of infection.

PMID 14576665  J Am Acad Dermatol. 2003 Nov;49(5):861-4. doi: 10.1067/・・・
著者: B F O'Donnell, D M Francis, G T Swana, P T Seed, A Kobza Black, M W Greaves
雑誌名: Br J Dermatol. 2005 Aug;153(2):331-5. doi: 10.1111/j.1365-2133.2005.06646.x.
Abstract/Text BACKGROUND: Chronic urticaria (CU) is an autoimmune process in some patients. An association between CU and autoimmune thyroid disease has also previously been proposed. Our group has identified functionally significant histamine-releasing autoantibodies in one subset of CU patients (subset 1), predicted by positive autologous intradermal serum tests and positive histamine release from donor basophil leucocytes in vitro. Sera from a second subset of patients (subset 2), all of whom had positive autologous intradermal serum tests, failed to release histamine from donor basophils. A final disease subset (subset 3) has no identifiable skin reactivity (negative autologous serum skin test) or in vitro histamine releasing activity.
OBJECTIVES: In order to examine further the possible relationships between thyroid autoimmunity, thyroid dysfunction and CU, we have examined thyroid autoantibodies and thyroid-stimulating hormone (TSH) levels (an indirect measure of thyroid dysfunction) in the three CU subsets.
PATIENTS/METHODS: We studied 182 patients (69% female), of whom 90 had a positive autologous intradermal serum test.
RESULTS: Eighteen skin test-positive and four skin test-negative patients had thyroid microsomal antibodies (TMA). TSH outside the normal range was found in 13 skin test-positive and one skin test-negative patient. These findings represent clustering of TMA positivity [risk ratio (RR) 4.06, 95% confidence interval (CI) 1.56-10.6] and of abnormal thyroid function (RR 15.5, CI 2.07-11.6) among the skin test-positive patients. However, in the overall study group an elevated TSH was present in seven patients (3.8%, CI 1.6-7.8) comparable to the 5% expected prevalence in the community. Thyroglobulin antibodies (TGA) were present in two of 182 patients.
CONCLUSIONS: There were significant differences between skin test-positive and skin test-negative patients with regard to autoimmune thyroid disease. Evidence for autoimmune thyroid disease and abnormal thyroid function was largely found among the skin test-positive patients, supporting the theory of an autoimmune aetiology in this group.

PMID 16086744  Br J Dermatol. 2005 Aug;153(2):331-5. doi: 10.1111/j.13・・・
著者: Shinsaku Fukuda, Tadashi Shimoyama, Noriko Umegaki, Tatsuya Mikami, Hajime Nakano, Akihiro Munakata
雑誌名: J Gastroenterol. 2004 Sep;39(9):827-30. doi: 10.1007/s00535-004-1397-7.
Abstract/Text BACKGROUND: Infection with Helicobacter pylori has been associated with chronic idiopathic urticaria (CIU). The aim of this study was to investigate the efficacy of H. pylori eradication in the treatment of patients with CIU.
METHODS: Fifty patients with CIU (16 men and 34 women; age 25-75 years) and 100 sex- and age-matched control subjects were enrolled in the study. Presence of IgG antibody to H. pylori was examined by serology. H. pylori-seropositive patients with CIU received endoscopy to confirm H. pylori infection. Patients infected with H. pylori received eradication therapy comprising lansoprazole, amoxicillin, and either clarithromycin or metronidazole. At least 2 months after finishing the eradication therapy, a (13)C-urea breath test was performed, and the effect of eradication therapy on the CIU was scored, using a three-point scale, as complete remission, partial remission, or no improvement.
RESULTS: In the 50 patients with CIU, 26 (52%) were H. pylori-seropositive, while 48% (48/100) of the control subjects were seropositive (statistically not significant). Nineteen out of the 26 patients with CIU infected with H. pylori received eradication therapy, and eradication was successful in 17 patients. In the 17 H. pylori-eradicated patients, 6 (35%) had complete remission and 11 (65%) had complete remission or partial remission. On the other hand, in the 9 patients without H. pylori eradication, only 2 (22%) showed partial remission and 7 (78%) had no improvement.
CONCLUSIONS: Eradication of H. pylori would be a valid choice for patients with CIU, although the prevalence of H. pylori infection is not higher in patients with CIU than it is in controls.

PMID 15565400  J Gastroenterol. 2004 Sep;39(9):827-30. doi: 10.1007/s0・・・
著者: Emel Bülbül Başkan, Tugba Türker, Macit Gülten, Sükran Tunali
雑誌名: Int J Dermatol. 2005 Dec;44(12):993-5. doi: 10.1111/j.1365-4632.2005.02280.x.
Abstract/Text BACKGROUND: There are controversial reports about the direct role of Helicobacterpylori infection in chronic idiopathic urticaria. The indirect role of H. pylori infection in the induction of pathogenetic antibodies is not fully elucidated either. This study aims to reveal the association of H. pylori infection with autologous serum skin test positivity in chronic idiopathic urticaria (CIU) patients.
METHODS: A total of 47 patients (35 women, 12 men, age range 17-65 years) diagnosed as CIU were included in the study. Autologous serum skin test was performed on all patients. The patients were examined with a commercially available ELISA test for H. pylori-specific antibodies. Gastroscopy with mucosal biopsy and rapid urease tests were proposed to verify the presence of H. pylori infection.
RESULTS: Helicobacter pylori infection was detected in 33 of the 47 patients (70%). No significant relation was found between the autologous serum skin test positivity and the serological and histopathological presence of H. pylori infection.
CONCLUSION: The results of our study suggest that chronic H. pylori infection does not appear to have a role in the induction of autoantibodies in CIU.

PMID 16409261  Int J Dermatol. 2005 Dec;44(12):993-5. doi: 10.1111/j.1・・・
著者: Asmaa Gaber Abdou, Elsayed I Elshayeb, Azza G A Farag, Nada Farag Elnaidany
雑誌名: Int J Dermatol. 2009 May;48(5):464-9. doi: 10.1111/j.1365-4632.2009.04042.x.
Abstract/Text BACKGROUND: Chronic urticaria is a persistent urticaria lasting longer than 6 weeks, affecting 20% of the general population. Various infectious agents have been reported as causes of urticaria, including Helicobacter pylori, which is a common worldwide bacterial infection. Its role in inducing allergic conditions, such as chronic urticaria, has been suggested in some reports and ignored in others.
AIMS: To assess the prevalence of H. pylori infection in patients with chronic urticaria and to explore the possible etiopathogenetic link between them.
METHODS: Thirty-five patients suffering from chronic urticaria and 10 normal control individuals were subjected to upper endoscopic gastric biopsies to assess and semiquantify H. pylori infection and to address other pathologic abnormalities, using routine hematoxylin and eosin staining and Giemsa staining.
RESULTS: Forty percent of control subjects and 57% of patients were positive for H. pylori infection, but the difference did not reach statistically significant levels (P = 0.47). The severity of urticarial symptoms was greater in the H. pylori-positive than in the H. pylori-negative group (P = 0.019). Heavy bacterial colonization (P = 0.008) and intense gastric inflammation (P < 0.0001) were associated significantly with severe clinical manifestations. Eighty percent of the H. pylori-positive urticaria group experienced complete remission after receiving eradication therapy for H. pylori.
CONCLUSIONS: Helicobacter pylori may have a role in the exacerbation of urticarial symptoms, even though it is not involved directly in its etiology, and its eradication may lead to symptom improvement in a considerable number of infected urticaria patients. The severity of symptoms is dependent on the density of bacterial infection and the intensity of inflammatory infiltrate in the gastric biopsy.

PMID 19416374  Int J Dermatol. 2009 May;48(5):464-9. doi: 10.1111/j.13・・・
著者: A Z Akelma, M N Cizmeci, E Mete, N Tufan, B Bozkurt
雑誌名: Allergol Immunopathol (Madr). 2015 May-Jun;43(3):259-63. doi: 10.1016/j.aller.2013.12.001. Epub 2014 Mar 20.
Abstract/Text BACKGROUND: The aetiology of chronic urticaria is usually considered idiopathic. There is a paucity of research both on the prevalence of Helicobacter pylori infection in the aetiology of chronic spontaneous urticaria (CU) in children and also on which patients H. pylori should be investigated.
METHODS: All paediatric and adult patients who presented to the allergy outpatient clinic due to CU between January 2011 and July 2012 were included in this prospective, randomised study. Stool samples from all patients were examined for the H. pylori antigen. Paediatric and adult patients who had a positive stool test for the H. pylori antigen were reassessed following eradication therapy.
RESULTS: Thirty-two children with CU and 35 adults with CU were enrolled in the study. Ten of the 32 (31.2%) children and 18 of the 35 (51.4%) adults were H. pylori positive (p=0.09). All children with positive-H. pylori were older than eight years of age. There was a significant positive correlation between age and the frequency of H. pylori infection (p<0.001; r=0.61). The presence of H. pylori was not significantly associated with the presence of GI (gastrointestinal) symptoms (p>0.05). Following H. pylori eradication, urticarial symptoms recovered in 15 of the adults (83.3%) and 10 of the paediatric (100%) patients (p=0.172).
CONCLUSION: In the current study we found that H. pylori is common among children with CU, particularly after eight years of age. We suggest that CU patients with an unknown aetiology should be routinely screened for H. pylori even if they do not present with GI symptoms and that those with H. pylori-positive results may receive treatment.

Copyright © 2013 SEICAP. Published by Elsevier Espana. All rights reserved.
PMID 24656622  Allergol Immunopathol (Madr). 2015 May-Jun;43(3):259-63・・・
著者: A Daschner, F Vega de la Osada, C Y Pascual
雑誌名: Allergol Immunopathol (Madr). 2005 Jan-Feb;33(1):31-7.
Abstract/Text BACKGROUND: The ubiquitous fish-nematode Anisakis simplex produces acute urticaria or angioedema in the course of gastro-allergic anisakiasis. We studied the relationship between this nematode and chronic urticaria (CU), as well as the clinical usefulness of measuring specific IgG4 in A. simplex-sensitized patients with CU.
METHODS: First, the prevalence of sensitization to A. simplex was estimated in 135 consecutive CU patients and the result was compared with known data about sensitization in a healthy population. Then, clinical response to a 2-month diet without fish was analyzed in 76 CU patients. The improvement rate in patients with and without sensitization to A. simplex was compared. Finally, the improvement rate, other clinical data and specific immunoglobulins in sensitized patients with and without detectable specific IgG4 were compared.
RESULTS: a) The A. simplex sensitization rate in CU patients was 52.6 % compared with a known prevalence of between 16 and 20 % in our region. b) Of 65 sensitized patients, 52 experienced clinical improvement after the diet compared with only three of 11 patients without sensitization to A. simplex (p = 0.001). c) Of 43 patients with detectable specific IgG4, 38 showed clinical improvement compared with only 14 of 22 patients without detectable IgG4 (p = 0.02). Eight of nine patients with previous fish-associated cutaneous symptoms had detectable specific IgG4 compared with 15 of 32 patients who reported no previous fish-associated symptoms or acute urticaria (p = 0.03).
CONCLUSIONS: Our results indicate that A. simplex is a possibly widespread etiologic agent able to induce CU. This parasite model constitutes the first report that associates an infectious agent with CU on a large scale. The detection of IgG4 antibodies reflects a previous acute parasitic infection and a temporary diet without fish improves symptoms in most patients with detectable specific IgG4.

PMID 15777521  Allergol Immunopathol (Madr). 2005 Jan-Feb;33(1):31-7.
著者: Sharma K Narasimha, C R Srinivas, Anil C Mathew
雑誌名: Int J Dermatol. 2005 May;44(5):425-7. doi: 10.1111/j.1365-4632.2005.02482.x.
Abstract/Text BACKGROUND: Very few studies have been conducted to assess the effect of corticosteroid application frequency to attain maximum benefit with minimum side-effects.
OBJECTIVES: Compare the efficacy of twice-daily, once-daily and alternate-day applications of clobetasol propionate (0.05%) and compare whether an initial once-daily application followed by a subsequent alternate-day application is as effective as a once-daily application.
METHODS: The ability of corticosteroids to suppress histamine-induced wheals on human skin was used as a human bioassay model. Of the 26 subjects included, 21 completed the 1st phase. In the 2nd phase, 11 subjects were included and all completed the study. Four sites were chosen on the left forearm. Clobetasol propionate (0.05%) was applied twice daily, once daily, and on alternate days, and on the control site a color, texture and odour-matched vehicle was applied. Prick test with histamine was carried out after 10 days. In the 2nd phase, clobetasol propionate (0.05%) was applied once daily for 14 days and compared with the initial once daily for 7 days and the subsequent alternate-day application for 7 days. Prick test was carried out after 14 days.
RESULTS: The once-daily application of clobetasol propionate (0.05%) was as effective as the twice-daily application, but the alternate-day application was less effective than the once-daily application (P < 0.01). Also, the initial-daily and subsequent alternate-day applications were not as effective as the continuous once-daily application (P < 0.05).
CONCLUSION: A once-daily application of clobetasol propionate (0.05%) is likely to provide the required therapeutic effect.

PMID 15869544  Int J Dermatol. 2005 May;44(5):425-7. doi: 10.1111/j.13・・・
著者: G A Vena, N Cassano, V D'Argento, M Milani
雑誌名: Br J Dermatol. 2006 Feb;154(2):353-6. doi: 10.1111/j.1365-2133.2005.06986.x.
Abstract/Text BACKGROUND: Delayed pressure urticaria (DPU) is characterized by the appearance of typical painful skin lesions (weals) after pressure stimulus. Oral corticosteroids are effective treatments but long-term therapy is problematic. A new topical formulation of clobetasol propionate 0.05% in thermophobic foam (CF) (Olux) has recently become available. The foam is easy to apply, with low skin residues.
OBJECTIVES: To evaluate in a double-blind placebo-controlled trial the efficacy, tolerability and safety of CF in the topical treatment of DPU.
METHODS: Twenty-six subjects with a positive history of DPU (13 men, mean age 44 years) were enrolled in a 4-week trial. CF or the corresponding placebo were applied twice daily. Drug application was performed in the most affected areas and in a target area where a standardized pressure challenge test was performed at baseline and at week 4. Efficacy was evaluated by scoring skin lesions regarding erythema, oedema and itching (0, no sign; 4, severe signs) and by calculating the area of the pressure challenge-induced lesion. Safety was evaluated by measuring plasma levels of adrenocorticotropic hormone (ACTH) and cortisol.
RESULTS: CF significantly (P = 0.0001) reduced lesion area by 84% in comparison with baseline values and by 97% in comparison with the placebo group values. Lesion area in the CF group was reduced from 144 cm(2) to 21 cm(2) at the end of the study. No significant differences in lesion area and clinical lesion scores were observed in the placebo group (lesion area 201 cm(2) at baseline; 216 cm(2) after 4 weeks). A significant clinical improvement was observed in all treated skin areas in the CF group. Mean +/- SD erythema score was reduced by CF from 1.8 +/- 0.6 at baseline to 0.6 +/- 0.5 at the end of the treatment (P = 0.001). Similar modifications were observed also for oedema (from 1.6 +/- 0.6 to 0.2 +/- 0.5) and itching score. Nonsignificant modifications of plasma levels of ACTH, cortisol and glucose were observed in both study groups, in comparison with baseline values. No adverse events were recorded during the trial in either treatment group.
CONCLUSIONS: CF is effective, safe, convenient and well tolerated in the short-term treatment of DPU.

PMID 16433809  Br J Dermatol. 2006 Feb;154(2):353-6. doi: 10.1111/j.13・・・
著者: F Etwel, N Djokanovic, M E Moretti, R Boskovic, J Martinovic, G Koren
雑誌名: J Obstet Gynaecol. 2014 Jul;34(5):392-9. doi: 10.3109/01443615.2014.896887. Epub 2014 Mar 28.
Abstract/Text Cetirizine, a second-generation antihistamine, is an active metabolite of hydroxyzine used in the treatment of allergies, but the data on fetal safety are inconclusive. Pregnant women who were counselled by the 'Motherisk Program' regarding cetirizine exposure were enrolled in a cohort study and compared with pregnant women counselled for non-teratogenic exposures. The objective was to measure the rate of adverse pregnancy outcomes. Subsequently, we also conducted a meta-analysis of cohort studies that examined the pregnancy outcomes of women exposed to hydroxyzine or cetirizine during pregnancy. In the cohort study, there were no significant differences in the rates of major malformations between the cetirizine exposed and comparison group. In the meta-analysis, cetirizine was not associated with increased teratogenic risk. In contrast, a meta-analysis of cetirizine and hydroxyzine studies showed a marginal association with major malformations. Cetirizine is not associated with a clinically important increase in risk of adverse fetal outcomes.

PMID 24678814  J Obstet Gynaecol. 2014 Jul;34(5):392-9. doi: 10.3109/0・・・
著者: Suzanne M Gilboa, Elizabeth C Ailes, Ramona P Rai, Jaynia A Anderson, Margaret A Honein
雑誌名: Expert Opin Drug Saf. 2014 Dec;13(12):1667-98. doi: 10.1517/14740338.2014.970164. Epub 2014 Oct 11.
Abstract/Text INTRODUCTION: Approximately 10 - 15% of women reportedly take an antihistamine during pregnancy for the relief of nausea and vomiting, allergy and asthma symptoms, or indigestion. Antihistamines include histamine H1-receptor and H2-receptor antagonists.
AREAS COVERED: This is a systematic evaluation of the peer-reviewed epidemiologic literature published through February 2014 on the association between prenatal exposure to antihistamines and birth defects. Papers addressing histamine H1- or H2-receptor antagonists are included. Papers addressing pyridoxine plus doxylamine (Bendectin in the United States, Debendox in the United Kingdom, Diclectin in Canada, Lenotan and Merbental in other countries) prior to the year 2001 were excluded post hoc because of several previously published meta-analyses and commentaries on this medication.
EXPERT OPINION: The literature on the safety of antihistamine use during pregnancy with respect to birth defects is generally reassuring though the positive findings from a few large studies warrant corroboration in other populations. The findings in the literature are considered in light of three critical methodological issues: i) selection of appropriate study population; ii) ascertainment of antihistamine exposures; and iii) ascertainment of birth defect outcomes. Selected antihistamines have been very well studied (e.g., loratadine); others, especially H2-receptor antagonists, require additional study before an assessment of safety with respect to birth defect risk could be made.

PMID 25307228  Expert Opin Drug Saf. 2014 Dec;13(12):1667-98. doi: 10.・・・
著者: J Hilbert, E Radwanski, M B Affrime, G Perentesis, S Symchowicz, N Zampaglione
雑誌名: J Clin Pharmacol. 1988 Mar;28(3):234-9.
Abstract/Text The excretion of loratadine, a new nonsedating antihistamine, into human breast milk was studied in six lactating nonpregnant volunteers. Each volunteer received one 40-mg loratadine capsule. Milk and blood were collected before and at specified times (to 48 hours) after dosing. Plasma and milk loratadine concentrations were determined by a specific radioimmunoassay, and those of an active but minor metabolite, descarboethoxyloratadine, by high performance liquid chromatography (HPLC). Breast milk concentration-time curves of both loratadine and descarboethoxyloratadine paralleled the plasma concentration-time curves. For loratadine, the plasma Cmax was 30.5 ng/mL at 1.0 hour after dosing and the milk Cmax was 29.2 ng/mL in the 0 to 2 hour collection interval. Through 48 hours, the loratadine milk-plasma AUC ratio was 1.2 and 4.2 micrograms of loratadine was excreted in breast milk, which was 0.010% of the administered dose. For descarboethoxyloratadine, the plasma Cmax was 18.6 ng/mL at 2.2 hours after dosing, whereas the milk Cmax was 16.0 ng/mL, which was in the 4 to 8-hour collection interval. Through 48 hours, the mean milk-plasma descarboethoxyloratadine AUC ratio was 0.8 and a mean of 6.0 micrograms of descarboethoxyloratadine (7.5 micrograms loratadine equivalents) were excreted in the breast milk, or 0.019% of the administered loratadine dose. Thus, a total of 11.7 micrograms loratadine equivalents or 0.029% of the administered dose were excreted as loratadine and its active metabolite. A 4-kg infant ingesting the loratadine and descarboethoxyloratadine excreted would receive a dose equivalent to 0.46% of the loratadine dose received by the mother on a mg/kg basis.(ABSTRACT TRUNCATED AT 250 WORDS)

PMID 2966185  J Clin Pharmacol. 1988 Mar;28(3):234-9.
著者: B D Lucas, C Y Purdy, S K Scarim, S Benjamin, S R Abel, D E Hilleman
雑誌名: Clin Pharmacol Ther. 1995 Apr;57(4):398-402. doi: 10.1016/0009-9236(95)90208-2.
Abstract/Text The excretion of terfenadine into breast milk has not been reported previously. Disposition of terfenadine was prospectively studied in four healthy lactating mothers (age, 33 +/- 4 years). Subjects received 60 mg terfenadine every 12 hours over a period of 48 hours to achieve steady-state milk and plasma concentrations. Milk and plasma samples were collected at 1/2, 1, 1 1/2, 2, 3, 4, 6, 8, 12, 24, and 30 hours after the last dose. Terfenadine and its active metabolite milk and plasma concentrations were quantitated by HPLC. Terfenadine was not detected in milk or plasma. Mean +/- SD active metabolite data for milk and plasma are as follows: Cmax (ng/ml), 41.0 +/- 16.4 for milk, 309.0 +/- 120.5 for plasma; tmax (hours), 4.3 +/- 2.4 for milk, 3.9 +/- 3.0 for plasma; t1/2 beta (hours), 14.2 +/- 5.4 for milk, 11.7 +/- 6.4 for plasma; AUC(0-12) (ng.hr/ml) 320.4 +/- 99.8 for milk, 1590.0 +/- 300.4 for plasma. Metabolite milk/plasmaAUC(0-12) ratios ranged from 0.12 to 0.28 (mean, 0.21 +/- 0.07). Newborn dosage estimates based on the highest measured concentration of terfenadine metabolite in milk suggests the maximum level of newborn exposure would not exceed 0.45% of the recommended maternal weight-corrected dose. Estimated amounts consumed by the neonate after the mother is given the recommended dose of the drug are not likely to result in plasma levels producing untoward effects.

PMID 7712667  Clin Pharmacol Ther. 1995 Apr;57(4):398-402. doi: 10.10・・・
著者: J P Spencer, L S Gonzalez, D J Barnhart
雑誌名: Am Fam Physician. 2001 Jul 1;64(1):119-26.
Abstract/Text Prescribing medications for a breast-feeding mother requires weighing the benefits of medication use for the mother against the risk of not breast-feeding the infant or the potential risk of exposing the infant to medications. A drug that is safe for use during pregnancy may not be safe for the nursing infant. The transfer of medications into breast milk depends on a concentration gradient that allows passive diffusion of nonionized, non-protein-bound drugs. The infant's medication exposure can be limited by prescribing medications to the breast-feeding mother that are poorly absorbed orally, by avoiding breast-feeding during times of peak maternal serum drug concentration and by prescribing topical therapy when possible. Mothers of premature or otherwise compromised infants may require altered dosing to avoid drug accumulation and toxicity in these infants. The most accurate and up-to-date sources of information, including Internet resources and telephone consultations, should be used.

PMID 11456429  Am Fam Physician. 2001 Jul 1;64(1):119-26.
著者: C V Pollack, T J Romano
雑誌名: Ann Emerg Med. 1995 Nov;26(5):547-51.
Abstract/Text STUDY OBJECTIVE: To evaluate the efficacy of a 4-day "burst" course of prednisone added to standard treatment with H1 antihistamines for the management of acute urticaria in outpatients.
DESIGN: Prospective, randomized, double-blinded, clinical trial.
SETTING: Emergency department of an urban tertiary care teaching hospital.
PARTICIPANTS: Adult patients with urticarial rash of no more than 24 hours' duration, regardless of cause. Patients were excluded if they manifested wheezing, stridor, or angioedema or if they had taken antihistamines or glucocorticoids within 5 days of arrival at the ED. Patients also were excluded if there was a history of diabetes or active peptic ulcer disease.
INTERVENTIONS: All patients were asked to evaluate the severity of pruritus ("itch score") on a 10-cm visual analog scale. Patients were then given diphenhydramine, 50 mg intramuscularly, and discharged home on a regimen of hydroxyzine, 25 mg orally, every 4 to 8 hours for pruritus, plus either prednisone, 20 mg, or placebo orally every 12 hours for 4 days. Patients' conditions were reassessed clinically, with itch score calculated again 2 days later, and again at 5 days by telephone.
RESULTS: Forty-three patients were enrolled; 24 received prednisone and 19 received placebo. The two groups had similar itch scores at enrollment (prednisone, 8.1 +/- 1.7; placebo, 7.4 +/- 2.1, P = .25 [ANOVA]), but at 2- and 5-day follow-up the prednisone group had significantly lower itch scores (1.3 +/- 1.3 and .0 +/- .0 versus 4.4 +/- 2.2 and 1.6 +/- 1.0, respectively; P < .0001 [ANCOVA] at each interval) and greater clinical improvement in rash. Response did not correlate with age, sex, or identification of an allergen. No adverse effects were noted in either group.
CONCLUSION: The addition of a prednisone burst improves the symptomatic and clinical response of acute urticaria to antihistamines. Patients' conditions improved more quickly and more completely when prednisone was administered, without any apparent adverse effects.

PMID 7486360  Ann Emerg Med. 1995 Nov;26(5):547-51.
著者: Yan-Ren Lin, Tzu-Hsuan Liu, Tung-Kung Wu, Yu-Jun Chang, Chu-Chung Chou, Han-Ping Wu
雑誌名: Am J Emerg Med. 2011 Oct;29(8):883-9. doi: 10.1016/j.ajem.2010.04.004. Epub 2010 Jul 13.
Abstract/Text PURPOSES: This study's aim was to determine the predictive factors of the duration of first-attack acute urticaria in children.
BASIC PROCEDURES: The sample included 1075 children admitted to the emergency department with first-attack acute urticaria. Variables comprising the clinical features and past histories of children with duration of disease of 3 days or less, 4 to 7 days, 8 to 14 days, and 15 days or more were compared to determine the predictors of duration of acute urticaria.
MAIN FINDINGS: Age, various etiologies, clinical presentations, coexistent pyrexia or angioedema, and personal histories of allergic diseases were significant factors (all P < .05). Among allergic diseases, atopic dermatitis was the most significant predictor of duration of acute urticaria, and those with multiple allergic diseases had longer durations of urticaria (both P < .05). Oral plus injection forms of antihistamine or steroid were related to shorter duration of disease (P < .05).
PRINCIPAL CONCLUSIONS: Etiologies and personal allergy history may be the most important predictors of the duration of a first attack of acute urticaria.

Copyright © 2011 Elsevier Inc. All rights reserved.
PMID 20627220  Am J Emerg Med. 2011 Oct;29(8):883-9. doi: 10.1016/j.aj・・・
著者: T Zuberbier, J Iffländer, C Semmler, B M Henz
雑誌名: Acta Derm Venereol. 1996 Jul;76(4):295-7.
Abstract/Text Although acute urticaria is common, its eliciting factors, clinical course and therapeutic responsiveness have not been intensively investigated. We have therefore prospectively studied all patients with acute urticaria attending the department of dermatology (n = 72) and a rural dermatology office (n = 37) during the course of 1 year. After a standardized history and physical examination, patients were randomized into treatment with either loratadine (10 mg/day for 3 days) or prednisolene (50 mg/day for 3 days). All patients were followed up until complete remission. Most patients suffered from moderate (42%) to severe (40%) disease. Possible eliciting factors were identified in less than 50% of the cases. Associated upper respiratory tract infections were found most commonly (39.5%), followed by possibly eliciting drugs, mostly analgesics (9.2%) and suspected food intolerance (0.9%). The course of the disease was self-limited in all cases, the longest episode lasting for 3 weeks. Both treatment regimens were effective in controlling whealing, but in corticosteroid-treated patients, symptoms ceased earlier, with complete remission occurring within 3 days of treatment in 93.8%, compared to 65.9% of patients treated with loratadine (p < 0.001). Acute urticaria is thus frequently idiopathic and only rarely associated with IgE-mediated events. It is, however, largely self-limited, with prompt response to symptomatic treatment.

PMID 8869688  Acta Derm Venereol. 1996 Jul;76(4):295-7.
著者: Caroline Barniol, Emilie Dehours, Jean Mallet, Charles-Henri Houze-Cerfon, Dominique Lauque, Sandrine Charpentier
雑誌名: Ann Emerg Med. 2018 Jan;71(1):125-131.e1. doi: 10.1016/j.annemergmed.2017.03.006. Epub 2017 May 3.
Abstract/Text STUDY OBJECTIVE: We evaluate the efficacy of a 4-day course of prednisone added to antihistamine for the management of acute urticaria in an emergency department (ED).
METHODS: In this double-blind randomized clinical trial, patients were eligible for inclusion if aged 18 years or older and with acute urticaria of no more than 24 hours' duration. Patients with anaphylaxis or who had received antihistamines or glucocorticoids during the previous 5 days were not included. In addition to levocetirizine (5 mg orally for 5 days), patients were assigned to receive prednisone (40 mg orally for 4 days) or placebo. The primary endpoint of the study was itching relief 2 days after the ED visit, rated on a numeric scale of 0 to 10. Secondary endpoints were rash resolution, relapses, and adverse events.
RESULTS: A total of 100 patients were included, 50 in each group. Seven patients in the prednisone group and 8 in the placebo group discontinued treatment. At 2-day follow-up, 62% of patients in the prednisone group had an itch score of 0 versus 76% of those in the placebo group (Δ 14%; 95% confidence interval -31% to 4%). Thirty percent of patients in the prednisone group and 24% in the placebo group reported relapses (Δ 6%; 95% confidence interval -23% to 11%). Mild adverse events were reported by 12% of patients in the prednisone group and 14% in the placebo group.
CONCLUSION: The addition of a prednisone burst did not improve the symptomatic and clinical response of acute urticaria to levocetirizine. This study does not support the addition of corticosteroid to H1 antihistamine as first-line treatment of acute urticaria without angioedema.

Copyright © 2017 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.
PMID 28476259  Ann Emerg Med. 2018 Jan;71(1):125-131.e1. doi: 10.1016/・・・
著者: D E Schuller, S M Elvey
雑誌名: Pediatrics. 1980 Mar;65(3):592-6.
Abstract/Text Eighty-one cases of acute urticaria were treated in our institution over a two-year period. In 13 of 32 cases screened for streptococcal pharyngitis, either positive throat culture, significant streptococcal exoenzyme antibodies (Streptozyme test), or both were found. Other causative factors for the acute urticaria had been excluded. It is our feeling that beta-hemolytic streptococcal infection may be a causative agent in many cases of acute urticaria, and that the infection may not always be clinically apparent. We therefore recommend a throat culture and determination of streptococcal enzyme level as routine procedures in evaluating acute urticaria. We also suggest, based on the findings in one case, that discontinuing therapy for a streptococcal infection when urticaria develops, even though necessary, might be inappropriate.

PMID 6987606  Pediatrics. 1980 Mar;65(3):592-6.
著者: Y Kameyoshi, T Tanaka, S Mihara, S Takahagi, N Niimi, M Hide
雑誌名: Br J Dermatol. 2007 Oct;157(4):803-4. doi: 10.1111/j.1365-2133.2007.08060.x. Epub 2007 Jul 11.
Abstract/Text
PMID 17627798  Br J Dermatol. 2007 Oct;157(4):803-4. doi: 10.1111/j.13・・・
著者: R Asero
雑誌名: Clin Exp Dermatol. 2007 Jan;32(1):34-8. doi: 10.1111/j.1365-2230.2006.02278.x. Epub 2006 Oct 16.
Abstract/Text Recently, several authors have suggested an off-label increase of antihistamine dosage should be given to patients with chronic urticaria (CU) not responding to the usual, recommended doses, in order to gain better control of the disease. However, this recommendation is not evidence-based. The objective of this study was to assess the effectiveness of increased doses of antihistamines in patients with CU showing poor control at recommended doses. In total, 22 adult patients with moderate/severe CU not controlled with the usual antihistamine doses were studied. These subjects recorded urticaria severity on a visual analogue scale (range 0-10) for 2 weeks. During the first week, they were treated with cetirizine at the licensed dose (10 mg/day), and with a three-fold increased dose (10 mg x 3/day) during week 2. Only 1 patient (5%) responded satisfactorily to the increased dosage of antihistamine; in the remaining 21 subjects, urticaria scores did not change, and these patients had to be treated with steroids, ciclosporin, and in 1 case with cyclophosphamide. Disease control was eventually gained in all cases. This study suggests that the proportion of patients with severe CU that may gain a better control of their disease with high, off-label doses of antihistamines is probably small, and that most patients will eventually have to undergo more aggressive treatments.

PMID 17042777  Clin Exp Dermatol. 2007 Jan;32(1):34-8. doi: 10.1111/j.・・・
著者: Karsten Weller, Claudia Ziege, Petra Staubach, Knut Brockow, Frank Siebenhaar, Karoline Krause, Sabine Altrichter, Martin K Church, Marcus Maurer
雑誌名: PLoS One. 2011;6(9):e23931. doi: 10.1371/journal.pone.0023931. Epub 2011 Sep 1.
Abstract/Text BACKGROUND: The guidelines recommend that first line treatment of chronic spontaneous urticaria should be second generation non-sedating H(1)-antihistamines with a positive recommendation against the use of old sedating first generation antihistamines. If standard dosing is not effective, increasing the dosage up to four-fold is recommended. The objective of this study was to obtain the chronic spontaneous urticaria-patient perspective on the effectiveness and unwanted effects of H(1)-antihistamines in standard and higher doses.
METHODOLOGY/PRINCIPAL FINDINGS: This was a questionnaire based survey, initially completed by 368 individuals. 319 (248 female, 71 male, median age 42 years) had a physician-confirmed diagnosis of chronic spontaneous urticaria and were included in the results. Participants believed standard doses (manufacturers recommended dose) of second generation antihistamines to be significantly (P<0.005) more effective than first generation drugs. Furthermore, they believed that second generation drugs caused significantly (P<0.001) fewer unwanted effects and caused significantly (P<0.001) less sedation than first generation antihistamines. Three-quarters of the patients stated that they had up-dosed with antihistamines with 40%, 42% and 54% reporting significant added benefit from taking 2, 3 or 4 tablets daily respectively. The number of reports of unwanted effects and sedation following up-dosing were not significantly different from those reported for standard doses.
CONCLUSIONS: This survey supports the urticaria guidelines recommendations that the first line treatment for chronic spontaneous urticaria should be second generation rather than first generation H(1)-antihistamines and that, if standard dosing is not effective, the dosage should be increased up to four-fold.

PMID 21909407  PLoS One. 2011;6(9):e23931. doi: 10.1371/journal.pone.0・・・
著者: Maria Staevska, Todor A Popov, Tanya Kralimarkova, Cvetelina Lazarova, Steliana Kraeva, Dora Popova, Diana S Church, Vasil Dimitrov, Martin K Church
雑誌名: J Allergy Clin Immunol. 2010 Mar;125(3):676-82. doi: 10.1016/j.jaci.2009.11.047.
Abstract/Text BACKGROUND: H(1)-antihistamines are first line treatment of chronic urticaria, but many patients do not get satisfactory relief with recommended doses. European guidelines recommend increased antihistamine doses of up to 4-fold.
OBJECTIVE: To provide supportive evidence for the European guidelines.
METHODS: Eighty tertiary referral patients with chronic urticaria (age range, 19-67 years) were randomized for double-blind treatment with levocetirizine or desloratadine (40/40). Treatment started at the conventional daily dose of 5 mg and then increased weekly to 10 mg, 20 mg, or 20 mg of the opposite drug if relief of symptoms was incomplete. Wheal and pruritus scores, quality of life, patient discomfort, somnolence, and safety were assessed.
RESULTS: Thirteen patients became symptom-free at 5 mg (9 levocetirizine vs 4 desloratadine), compared with 28 subjects on the higher doses of 10 mg (8/7) and 20 mg (5/1). Of the 28 patients nonresponsive to 20 mg desloratadine, 7 became symptom-free with 20 mg levocetirizine. None of the 18 levocetirizine nonresponders benefited with 20 mg desloratadine. Increasing antihistamine doses improved quality of life but did not increase somnolence. Analysis of the effect of treatment on discomfort caused by urticaria showed great individual heterogeneity of antihistamine responsiveness: approximately 15% of patients were good responders, approximately 10% were nonresponders, and approximately 75% were responders to higher than conventional antihistamine doses. No serious or severe adverse effects warranting discontinuation of treatment occurred with either drug.
CONCLUSION: Increasing the dosage of levocetirizine and desloratadine up to 4-fold improves chronic urticaria symptoms without compromising safety in approximately three quarters of patients with difficult-to-treat chronic urticaria.

PMID 20226302  J Allergy Clin Immunol. 2010 Mar;125(3):676-82. doi: 10・・・
著者: T Zuberbier, W Aberer, R Asero, A H Abdul Latiff, D Baker, B Ballmer-Weber, J A Bernstein, C Bindslev-Jensen, Z Brzoza, R Buense Bedrikow, G W Canonica, M K Church, T Craig, I V Danilycheva, C Dressler, L F Ensina, A Giménez-Arnau, K Godse, M Gonçalo, C Grattan, J Hebert, M Hide, A Kaplan, A Kapp, C H Katelaris, E Kocatürk, K Kulthanan, D Larenas-Linnemann, T A Leslie, M Magerl, P Mathelier-Fusade, R Y Meshkova, M Metz, A Nast, E Nettis, H Oude-Elberink, S Rosumeck, S S Saini, M Sánchez-Borges, P Schmid-Grendelmeier, P Staubach, G Sussman, E Toubi, G A Vena, C Vestergaard, B Wedi, R N Werner, Z Zhao, M Maurer, Endorsed by the following societies: AAAAI, AAD, AAIITO, ACAAI, AEDV, APAAACI, ASBAI, ASCIA, BAD, BSACI, CDA, CMICA, CSACI, DDG, DDS, DGAKI, DSA, DST, EAACI, EIAS, EDF, EMBRN, ESCD, GA²LEN, IAACI, IADVL, JDA, NVvA, MSAI, ÖGDV, PSA, RAACI, SBD, SFD, SGAI, SGDV, SIAAIC, SIDeMaST, SPDV, TSD, UNBB, UNEV and WAO
雑誌名: Allergy. 2018 Jul;73(7):1393-1414. doi: 10.1111/all.13397.
Abstract/Text This evidence- and consensus-based guideline was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. The conference was held on 1 December 2016. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the EU-founded network of excellence, the Global Allergy and Asthma European Network (GA²LEN), the European Dermatology Forum (EDF) and the World Allergy Organization (WAO) with the participation of 48 delegates of 42 national and international societies. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease, presenting with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic forms of urticaria are disabling, impair quality of life and affect performance at work and school. This guideline covers the definition and classification of urticaria, taking into account the recent progress in identifying its causes, eliciting factors and pathomechanisms. In addition, it outlines evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.

© 2018 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.
PMID 29336054  Allergy. 2018 Jul;73(7):1393-1414. doi: 10.1111/all.133・・・
著者: S Guillén-Aguinaga, I Jáuregui Presa, E Aguinaga-Ontoso, F Guillén-Grima, M Ferrer
雑誌名: Br J Dermatol. 2016 Dec;175(6):1153-1165. doi: 10.1111/bjd.14768. Epub 2016 Oct 19.
Abstract/Text There is a lack of large, randomized, double-blind studies that address antihistamine updosing for chronic spontaneous urticaria (CSU). The objective of this systematic review is to explore and analyse available data to provide clinical evidence for the efficacy of antihistamine updosing. We searched the literature in Medline, Scopus, Google Scholar, Embase, Web of Science and Cochrane databases using the keywords 'chronic, urticaria, antihistamines' to identify studies published between January 1990 and November 2014. We assessed quality using the Jadad score that evaluates quality of randomization, double-blinding and losses to follow-up. We identified 1042 articles and 15 articles were included in the final evaluation. We performed two meta-analyses, one that included studies that analysed treatment response among groups receiving different antihistamine dosages vs. placebo, and another that analysed antihistamine updosing in those patients who did not respond to standard dosages. Only five articles obtained a high quality level score. We did not find significant differences in response rates or number of weals in those patients who received a standard dosage vs. a high dosage. We found a significant improvement only in the pruritus variable of the Urticaria Activity Score scale. The estimated relative risk for improvement by increasing the antihistamine dosage was 2·27 [95% confidence interval (CI) 1·68-3·06]; however, there was significant heterogeneity. The proportion of nonrespondent patients with CSU who responded to antihistamine updosing was 63·2% (95% CI 57-69·6). We found that updosing antihistamines significantly improved control of pruritus but not weal number. However, the relative weakness of the studies and the significant heterogeneity among them made it difficult to reach a final conclusion.

© 2016 British Association of Dermatologists.
PMID 27237730  Br J Dermatol. 2016 Dec;175(6):1153-1165. doi: 10.1111/・・・
著者: E W Monroe, S H Cohen, J Kalbfleisch, C I Schulz
雑誌名: Arch Dermatol. 1981 Jul;117(7):404-7.
Abstract/Text Chronic urticaria is a frustrating problem for the patient and the physician. The cause is usually undetermined, and the therapy is directed toward controlling symptoms. Recent evidence that human skin blood vessels possess H2 receptors, as well as the commonly recognized H1 receptors, suggests a possible reason for the frequent failure of H1 antihistamines in controlling this disorder. Eighteen patients with refractory chronic idiopathic urticaria participated in a double-blind, cross-over study to evaluate the efficacy of combined H1 (hydroxyzine hydrochloride) and H2 (cimetidine) antihistamines vs H1 antihistamines alone. This study indicates that combined H1 and H2 antihistamine therapy is statistically more effective than H1 antihistamines alone in controlling the symptoms of chronic urticaria.

PMID 6114712  Arch Dermatol. 1981 Jul;117(7):404-7.
著者: S S Bleehen, S E Thomas, M W Greaves, J Newton, C T Kennedy, F Hindley, R Marks, M Hazell, N R Rowell, G M Fairiss
雑誌名: Br J Dermatol. 1987 Jul;117(1):81-8.
Abstract/Text One hundred and twenty patients with chronic idiopathic urticaria, who entered a study at five centres (Sheffield, London, Bristol, Cardiff and Leeds) were treated with therapeutic doses of the H1 antagonist chlorpheniramine for 6 weeks. Histamine H1 non-responders (40 patients) were entered into a double-blind study and received chlorpheniramine plus cimetidine 400 mg q.d.s. (21 patients) or chlorpheniramine plus placebo (19 patients) for a further 8 weeks. The most important response measure was the change from baseline of the total symptom score: an assessment of the number and duration of new weals and degree of itching. There was a statistically significant difference between the average response in the two treatment groups in favour of chlorpheniramine plus cimetidine after 4 and 8 weeks' treatment (P less than 0.05 and P less than 0.01, respectively). No significant side-effects related to treatment were noted.

PMID 3307890  Br J Dermatol. 1987 Jul;117(1):81-8.
著者: E Paul, R H Bödeker
雑誌名: Eur J Clin Pharmacol. 1986;31(3):277-80.
Abstract/Text 45 patients with chronic urticaria were randomized to double blind therapy with terfenadine an H1-antihistamine or ranitidine, an H2-antihistamine, or a combination of both drugs. The therapeutic response was assessed by diary scores. The primary effect variable was "itching". The inference-statistical evaluation of the patient scores showed varying therapeutic effects. The Type-I error was p = 0.015. Itching was reported to be significantly lower by patients receiving both drugs than by those who were given terfenadine alone, while ranitidine in monotherapy had no significant effect on itching. A similar trend was seen in assessment of the severity of weals, while the treatment regimens had no influence on swelling.

PMID 2878811  Eur J Clin Pharmacol. 1986;31(3):277-80.
著者: F E Simons, G L Sussman, K J Simons
雑誌名: J Allergy Clin Immunol. 1995 Mar;95(3):685-93.
Abstract/Text BACKGROUND: Concomitant administration of an H1-receptor antagonist with an H2-receptor antagonist may enhance the wheal and flare suppression produced by the H1-antagonist. This synergism may be due, at least in part, to a pharmacokinetic effect.
METHODS: In a randomized, double-blind, parallel-group study in 16 patients with chronic urticaria, we investigated the pharmacokinetics and suppressive effect on the histamine-induced wheal and flare of a single dose of hydroxyzine 25 mg or cetirizine 10 mg, given before and after treatment with cimetidine 600 mg every 12 hours for 10 days.
RESULTS: When hydroxyzine was administered with cimetidine, the partial hydroxyzine area under the curve increased significantly (p < 0.05) to 303 +/- 92 ng/ml/hr from 227 +/- 77 ng/ml/hr after administration of hydroxyzine alone, and the concentration of cetirizine arising from hydroxyzine was lower. When hydroxyzine was given with cimetidine, wheal and flare suppression increased compared with when hydrozyzine was given alone, but the differences were not statistically significant (p > 0.05). When cetirizine was administered with cimetidine, the pharmacokinetics of cetirizine did not change significantly, and no enhancement of wheal and flare suppression was observed.
CONCLUSIONS: In this study co-administration of hydroxyzine with cimetidine resulted in significantly increased serum hydroxyzine concentrations and increased wheal and flare suppression, thus confirming the rationale for a trial of concomitant administration of these medications in some patients with chronic urticaria unresponsive to treatment with an H1-antagonist alone. We found no therapeutic rationale for co-administration of cetirizine with cimetidine in urticaria treatment. These medications may be co-administered safely without fear of medication interaction.

PMID 7897151  J Allergy Clin Immunol. 1995 Mar;95(3):685-93.
著者: C A Commens, M W Greaves
雑誌名: Br J Dermatol. 1978 Dec;99(6):675-9.
Abstract/Text
PMID 367422  Br J Dermatol. 1978 Dec;99(6):675-9.
著者: L J Cook, S Shuster
雑誌名: Acta Derm Venereol. 1983;63(3):265-7.
Abstract/Text The effect of an H1 and an H2 receptor blocker singly and in combination was studied in 20 patients with chronic idiopathic urticaria. Both H1 receptor blockade alone and in combination with H2 receptor blockade produced a significant reduction in wealing and itch; there was no significant difference between these treatments. H2 blockade alone produced no significant reduction in wealing; there was a slight increase in itch, though not statistically significant.

PMID 6192652  Acta Derm Venereol. 1983;63(3):265-7.
著者: Elizabeth Guevara-Gutierrez, Sonia Bonilla-Lopez, Socorro Hernández-Arana, Alberto Tlacuilo-Parra
雑誌名: J Dermatolog Treat. 2015;26(6):548-50. doi: 10.3109/09546634.2015.1025031. Epub 2015 Apr 17.
Abstract/Text BACKGROUND: First-line treatment for chronic urticaria is H1 non-sedating antihistamines. When these fail, guidelines recommend combination with H2 antihistamines.
AIM: We conducted a randomized, double-blind, placebo-controlled trial.
METHODS: Thirty-two patients with chronic urticaria were included. Group A (16 subjects) treated with cetirizine plus ranitidine and Group B (16 subjects) with cetirizine plus placebo, both for 30 days. Efficacy measures were Urticaria Activity Score (UAS), Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL) and time of symptom remission, safety measures were clinical and laboratory effects.
RESULTS: Complete remission was obtained in ten patients (62.5%) from Group A and seven patients (44%) from Group B (p = 0.28). The UAS in Group A was 1.53 ± 2.09 versus Group B 2.06 ± 1.34 (p = 0.20). The CU-Q2oL in Group A was 12.93 ± 19.20 versus Group B 12.68 ± 10.30 (p = 0.20). At the end of treatment, 13 patients (81%) from Group A and 14 patients (87.5%) from Group B had some type of adverse effect (p = 1.0).
CONCLUSIONS: Combination of cetirizine with ranitidine was not more effective than cetirizine alone in chronic urticaria. Both treatments resulted equally safe; however, our main limitation is the small sample size.

PMID 25886090  J Dermatolog Treat. 2015;26(6):548-50. doi: 10.3109/095・・・
著者: Yumi Ogawa, Yuko Ichinokawa, Midori Hiruma, Yuko Machida, Naoko Funakushi, Hiroko Sadamasa, Masataro Hiruma
雑誌名: J Dermatolog Treat. 2013 Dec;24(6):463-5. doi: 10.3109/09546634.2013.800183. Epub 2013 May 21.
Abstract/Text We conducted a retrospective cohort study evaluating the efficacy and usefulness of the addition of lafutidine, a novel histamine H2-receptor antagonist, in treatment of patients with idiopathic chronic urticaria whose disease was not well controlled with histamine H1-receptor antagonists. Based on the assessment of global improvement, moderate or better improvement was achieved in 39 of 46 patients (85%) after 1-3 weeks of additional administration of lafutidine and 35 patients (76%) after 3 months. No incidence of drug-related adverse reactions was reported in any patient. Lafutidine was rated as useful or better in 34 patients (74%) after 3 months of treatment. The usefulness of the drug was not affected by differences in background factors, such as disease duration, previous treatment duration and the number of concomitant H1-receptor antagonists. Lafutidine appears to be a promising addition to histamine H1-receptor antagonist therapy for the treatment of chronic urticaria resistant to treatment with H1-receptor antagonists alone.

PMID 23639034  J Dermatolog Treat. 2013 Dec;24(6):463-5. doi: 10.3109/・・・
著者: E Nettis, M C Colanardi, M T Paradiso, A Ferrannini
雑誌名: Clin Exp Allergy. 2004 Sep;34(9):1401-7. doi: 10.1111/j.1365-2222.2004.02019.x.
Abstract/Text BACKGROUND: Chronic urticaria (CU) is a common skin condition. It is frequently a disabling disease due to the persistency of clinical symptoms, the unpredictable course and negative influence on the quality of life.
OBJECTIVE: The aim of this study is to determine whether montelukast, a LTD4 receptor antagonist, plus desloratadine, is more efficacious than desloratadine alone in the treatment of chronic urticaria.
MATERIALS: A randomized, double-blind, placebo-controlled study was conducted on 81 patients with a diagnosis of CU. A 1-week single-blind placebo run-in period (baseline) was followed by a 6-weeks double blind active treatment period. The patients were randomized to receive the following treatment once daily: (a) oral desloratadine (5 mg) plus placebo; (b) desloratadine (5 mg) plus montelukast (10 mg); (c) oral placebo alone. The study ended after another 1-week single-blind placebo washout period.
RESULTS: The evaluable population thus consisted of 76 patients. Both desloratadine alone and desloratadine plus montelukast administered once daily yielded improvements with respect to the baseline assessment as regards pruritus, number of separate episodes, size and number of weals, visual analogue score and patients' quality of life and with respect to the placebo group both in the active treatment period and in the run-out period. However, desloratadine plus montelukast was shown to improve the symptoms and patients' quality of life significantly more than desloratadine alone, although it did not have a significant effect on the number of urticarial episodes.
CONCLUSION: The combination of desloratadine plus montelukast is effective in the treatment of CU. It may therefore be a valid alternative in patients with relatively mild CU, in view of its efficacy and the lack of adverse events.

PMID 15347373  Clin Exp Allergy. 2004 Sep;34(9):1401-7. doi: 10.1111/j・・・
著者: Gabriele Di Lorenzo, Maria Luisa Pacor, Pasquale Mansueto, Maria Esposito Pellitteri, Claudia Lo Bianco, Vito Ditta, Nicola Martinelli, Giovam Battista Rini
雑誌名: J Allergy Clin Immunol. 2004 Sep;114(3):619-25. doi: 10.1016/j.jaci.2004.06.018.
Abstract/Text BACKGROUND: H 1 -receptor antagonists are considered to be particularly effective in reducing pruritus, and they are therefore recommended as first-line treatment in patients with chronic idiopathic urticaria (CIU). Recently, antileukotriene receptors have been used in patients with CIU, either administered as monotherapy or combined with H 1 -receptor antagonists.
OBJECTIVE: We compared the clinical efficacy of 5 mg of desloratadine administered once daily either as monotherapy or combined with a leukotriene antagonist, 10 mg of montelukast daily, and 10 mg of montelukast administered daily as monotherapy for the treatment of patients affected by CIU with placebo.
METHODS: One hundred sixty patients aged 18 to 69 years (mean +/- SD, 43.9 +/- 13.4 years) with a history of moderate CIU were selected. A randomized, double-blind, double-dummy, placebo-controlled, parallel-group study design was used. Patients were treated with 5 mg of desloratadine once daily (n = 40), 10 mg of montelukast once daily (n = 40), 5 mg of desloratadine (n = 40) in the morning plus montelukast in the evening, or matched placebo (n = 40). Assessment of treatment efficacy was based on scores of daily cutaneous symptoms evaluated reflectively and instantaneously.
RESULTS: Only the group treated with desloratadine as monotherapy or as combined therapy concluded the whole study. Twenty-seven of the 40 patients in the montelukast group and 35 of the 40 patients in the placebo group discontinued the treatment. As reflective evaluation, all groups showed significant differences compared with the placebo group in terms of total symptom score, number of hives, and size of largest hive. In addition to the pruritus, only the groups treated with desloratadine as monotherapy or combined therapy showed significant differences compared with those receiving placebo, whereas there were no differences between the montelukast and placebo groups. Finally, no differences were found between the desloratadine group and the desloratadine plus montelukast group. The instantaneous evaluation demonstrated similar results regarding the desloratadine group and the desloratadine plus montelukast group versus the placebo group, whereas there were no significant differences between the group treated with montelukast alone and the placebo group for pruritus and size of largest hive. No differences were found between the group treated with desloratadine alone and the desloratadine plus montelukast group.
CONCLUSIONS: The results of this comparative study demonstrate that desloratadine is highly effective for the treatment of patients affected by CIU. In addition, the regular combined therapy of desloratadine plus montelukast does not seem to offer a substantial advantage with respect to desloratadine as monotherapy in patients affected by moderate CIU.

PMID 15356567  J Allergy Clin Immunol. 2004 Sep;114(3):619-25. doi: 10・・・
著者: Seiko Sanada, Toshihiko Tanaka, Yoshikazu Kameyoshi, Michihiro Hide
雑誌名: Arch Dermatol Res. 2005 Sep;297(3):134-8. doi: 10.1007/s00403-005-0586-4. Epub 2005 Sep 29.
Abstract/Text Many patients with chronic idiopathic urticaria are not sufficiently controlled with histamine H(1)-receptor antagonists. Leukotriene receptor antagonists have been reported to be effective for certain cases of urticaria, although their proper application remains to be established. To study the effectiveness of montelukast, a leukotriene receptor antagonist, for the treatment of chronic urticaria that was not controlled by histamine H(1)-receptor antagonists. Twenty-five patients with chronic idiopathic urticaria were treated with 10 mg of montelukast for one week or more, without changing any precedent treatment that they were using before the study including histamine H(1)-receptor antagonists. The effectiveness of montelukast for each patient was evaluated and compared with clinical features and/or backgrounds of the patients. Twelve patients, including six who had been treated with corticosteroids, were evaluated as "markedly improved" or "improved" following treatment with montelukast. There was no statistically significant relation of the effectiveness to the complications with non-steroidal anti-inflammatory drugs (NSAIDs) intolerance, mechanical urticaria, or reactions to autologous serum skin test. However, the patients for whom montelukast was effective were younger (33.2+/-16.3 years, mean +/- SD)(P<0.05, Mann-Whitney test) and their duration of illness shorter (15.9+/-18.3 months) (P<0.005, Mann-Whitney test) than those of patients for whom montelukast was ineffective (45.9+/-15.0 years, 89.6+/-71.7 months). Montelukast may be worth trying for patients with chronic idiopathic urticaria, when the condition is not sufficiently controlled with histamine H(1)-receptor antagonists.

PMID 16044256  Arch Dermatol Res. 2005 Sep;297(3):134-8. doi: 10.1007/・・・
著者: Zülal Erbagci
雑誌名: J Allergy Clin Immunol. 2002 Sep;110(3):484-8.
Abstract/Text BACKGROUND: Chronic idiopathic urticaria (CIU) might be refractory to standard therapies. For the patients with severe unremitting CIU who have failed to benefit from conventional therapy with antihistamines, other effective and safe therapeutic modalities are required.
OBJECTIVE: A randomized, single-blind, placebo-controlled crossover study was conducted to evaluate the efficacy and safety of the new selective leukotriene antagonist montelukast sodium in the treatment of refractory CIU.
METHODS: Thirty patients with refractory CIU were enrolled in the trial. After informed consent was obtained, patients were randomly assigned to 2 groups. The patients in group A received 10 mg/d montelukast and a nonsedating H(1) antihistamine (cetirizine) when needed for 6 weeks. After a 2-week washout period, they received placebo for 6 weeks and the same H(1) antihistamine as needed. Group B received the treatment vice versa. Improvement was monitored by using the self-estimated urticaria activity score, which is the sum of the wheal number score and the itch severity score, and the antihistamine counts used in each study period.
RESULTS: More significant decreases occurred in urticaria activity scores with montelukast therapy compared with those with placebo therapy (P <.001). H(1) antihistamine use was also significantly less frequent during the montelukast period (P <.001). There were no significant side effects with montelukast therapy.
CONCLUSION: The present study results suggest that montelukast might be an effective and safe therapeutic agent in the treatment of refractory CIU.

PMID 12209099  J Allergy Clin Immunol. 2002 Sep;110(3):484-8.
著者: Mitja Kosnik, Tjasa Subic
雑誌名: Respir Med. 2011 Oct;105 Suppl 1:S84-8. doi: 10.1016/S0954-6111(11)70018-X.
Abstract/Text BACKGROUND: Antihistamines (AH) alleviate pruritus and decrease the incidence of hives in patients with chronic idiopathic urticaria (CU). However, some patients do not respond completely to this therapy. We hypothesized that some of them might benefit from the addition of leukotriene receptor antagonists (LA).
METHODS: We screened patients diagnosed and treated for CU and selected those that had symptoms despite antihistamine treatment. In a double-blind crossover study, patients took the leukotriene antagonist montelukast (10 mg per day) or placebo. Efficacy was assessed by a symptom score.
RESULTS: In a group of 22 patients, the symptom score was not significantly different between periods using montelukast (48.8; 0-214) or placebo (68.5; 0-230). However in the subgroup of five patients with the most severe urticaria, defined as patients with symptom scores in the upper quartile at inclusion in the study, montelukast (41; 11 214) was superior to placebo (95.5; 48 230; p < 0.05), but only when using an in-house symptom score questionnaire and not when using a validated urticaria activity score questionnaire.
CONCLUSIONS: We showed that in patients with antihistamine-resistant CU the addition of montelukast significantly diminished symptoms in only a small minority of patients. However, response to add-on montelukast was seen in the subgroup of patients with particularly severe disease. To confirm this observation, a study with a larger group of patients is warranted.

Copyright © 2011 Elsevier Ltd. All rights reserved.
PMID 22015095  Respir Med. 2011 Oct;105 Suppl 1:S84-8. doi: 10.1016/S0・・・
著者: Scott E Bagenstose, Linda Levin, Jonathan A Bernstein
雑誌名: J Allergy Clin Immunol. 2004 Jan;113(1):134-40. doi: 10.1016/j.jaci.2003.10.002.
Abstract/Text BACKGROUND: Because leukotrienes have potent local effects on cutaneous vasculature, leukotriene antagonists might be effective in the treatment of chronic urticaria.
OBJECTIVE: A double-blinded, placebo-controlled trial comparing cetirizine 10 mg daily in combination with zafirlukast 20 mg twice a day versus cetirizine 10 mg daily and placebo was conducted to determine whether subjects with chronic urticaria benefit from add-on therapy with a leukotriene-modifying agent.
METHODS: Patients 12 years or older with a history of chronic urticaria (more than 6 weeks in duration) required diary documentation of 6 or more hives on at least 2 days/week and a suboptimal response to H(1)-antagonist therapy for enrollment. At baseline, all subjects were skin tested to autologous serum to assess for the potential presence of FcepsilonRI or IgE autoantibodies. Subjects meeting the initial entry criteria were treated with cetirizine 10 mg a day and placebo twice daily for 1 week. Those patients with persistent hives were randomized to receive cetirizine 10 mg daily and zafirlukast 20 mg twice a day or cetirizine 10 mg daily and placebo. At each successive weekly visit, physician and patient treatment effectiveness score (TES) and visual analog scale (VAS) ratings were recorded. Statistical analysis used generalizing estimating equations to compare the effect of combination therapy versus monotherapy on TES and VAS ratings. Results were adjusted for baseline rating, recruiting center, and autologous serum skin test (ASST). A separate analysis evaluated patients with positive ASST results receiving combination therapy versus monotherapy.
RESULTS: Combination therapy with zafirlukast demonstrated a modest but significantly greater improvement compared with cetirizine monotherapy in physician and patient recorded VAS ratings at visit 4 and across treatment visits 4 through 6 (P <.05 unless stated otherwise). Subjects with ASST positive results receiving combination therapy as compared with subjects with negative ASST results exhibited a significant improvement in patient recorded VAS ratings across visits 4 through 6. Subgroup analysis of subjects with ASST positive results receiving combination therapy versus monotherapy showed improvement in physician recorded TES at visit 5, physician recorded VAS at visits 4 and 5 and across visits 4 through 6, as well as for patient recorded VAS at visit 5. There were no significant results for patients with ASST negative results.
CONCLUSION: The results of this study indicate that only patients with autoimmune (ASST positive) chronic urticaria refractory to H(1)-antagonist monotherapy might benefit from the addition of the leukotriene D(4)-receptor antagonist zafirlukast to their treatment regimen. These results also suggest that routine screening of patients with chronic urticaria with the ASST might be useful in formulating therapeutic algorithms in the management of chronic urticaria.

PMID 14713918  J Allergy Clin Immunol. 2004 Jan;113(1):134-40. doi: 10・・・
著者: M L Pacor, G Di Lorenzo, R Corrocher
雑誌名: Clin Exp Allergy. 2001 Oct;31(10):1607-14.
Abstract/Text BACKGROUND: The cause and pathogenesis of chronic urticaria are still poorly understood. IgE-independent reactions, are common in adult patients with chronic urticaria, who have daily spontaneous occurrence of weals. H(1)-receptor antagonists (antihistamines) are the major class of therapeutic agents used in the management of urticaria and angioedema. Nevertheless, chronic urticaria is often difficult to treat and may not be controlled by antihistamines alone. It has been postulated that mediators other than histamine, such as kinins, prostaglandin and leukotrienes, may be responsible for some of the symptoms in urticaria which are not controlled by antihistamines. In this study, which was randomized double-blind, placebo-controlled, we compare the clinical efficacy and safety of montelukast (MT) 10 mg given once a day and cetirizine (CET) 10 mg given once a day with placebo (PLA), in the treatment of patients with chronic urticaria who have positive challenge to acetylsalicylic acid (ASA) and/or food additives.
PATIENTS AND METHODS: A group of 51 patients, ranging in age from 15 to 71 years, with chronic urticaria and positive challenge to food additives and/or ASA, participated in this study for a period of 4 weeks, starting from a 3-day run-in. The assessment of the efficacy was based on scores of daily urticaria symptoms.
RESULTS: MT significantly increased the percentage of symptom-free days for hive and itch. Analysis of frequency distribution of urticaria scores for each symptom gave similar results (MT vs. CET and MT vs. PLA, P < 0.001). The interference with sleep due to their skin condition was also lower in the group treated with MT (P < 0.001). In addition, the median number of days without the rescue medication was significantly higher in the MT group (24 days) than both the CET and the PLA groups (18 days, P < 0.001, and 20 days, P < 0.001, respectively). Finally, a low incidence of adverse events was observed in this study.
CONCLUSION: The results of this comparative study demonstrate that montelukast orally administered once a day is very effective for the treatment of cutaneous symptoms in patients with chronic urticaria due to food additives and/or ASA.

PMID 11678862  Clin Exp Allergy. 2001 Oct;31(10):1607-14.
著者: Kong-Sang Wan, Yung-Sen Chang
雑誌名: J Dermatolog Treat. 2014 Dec;25(6):459-61. doi: 10.3109/09546634.2013.849791. Epub 2013 Nov 5.
Abstract/Text BACKGROUND: The efficacy of the combination of leukotriene receptor antagonist (LRA) and H1 antihistamine was similar to the synergistic regimen of H1 and H2 antihistamine for treatment of chronic idiopathic urticaria (CIU). However, the effective rates of these two regimens were only 53.3% and 63.3%, respectively.
METHOD: A total of 50 with two combined therapeutic regimens treatment ineffective patients were evaluated. Patients were single blinded and randomly assigned to one of two medication groups that received the following regimens for 4 weeks: Group A (n = 30), combination of LRA, H1 antihistamine and H2 antihistamine. Group B (n = 20) continued with the previously taken two combination regimens. The treatment efficacy was measured by daily urticaria activity score (UAS) of wheal and itch. A positive therapeutic response was defined as a reduction to <25% of baseline weekly UAS, while a relapse was a return to >75% of baseline weekly UAS.
RESULTS: At the end of 4 weeks, the UAS response to treatment of Group A was decreased from 35.2% to 21.2%, and the Group B was persisted with 33.9% as before the treatment.
CONCLUSION: The combination of LRA, H2 antihistamine and H1 antihistamine is promising for the refractory CIU cases, which were refractory for two combined therapeutic regimens.

PMID 24192062  J Dermatolog Treat. 2014 Dec;25(6):459-61. doi: 10.3109・・・
著者: Sujoy Khan, Nuala Lynch
雑誌名: Inflamm Allergy Drug Targets. 2012 Jun;11(3):235-43.
Abstract/Text Chronic idiopathic urticaria is a common skin disorder characterized by recurrent appearance of wheals and/or angioedema for more than 6 weeks without an identifiable cause. Consensus guidelines suggest use of leukotriene receptor antagonists (montelukast or zafirlukast) in patients whose urticaria is resistant to antihistamines. Our objectives were (1) document the efficacy of montelukast in our patients, and (2) evaluate whether any clinical features or available laboratory investigations were associated with a response to montelukast. Patients who received montelukast between the years 2008-2011 (4-year period) were retrospectively identified from clinic letters. Clinical features and laboratory investigations were collected and analyzed. The primary end point was adequate control of disease without the need for systemic steroid therapy. 25 patients (10 males and 15 females; median age, 33 years; age range, 13-66 years) with an average duration of urticaria at 3.8 years received montelukast 10mg daily. 12 patients (48%) were better on montelukast with combined anti-H1 and anti-H2 therapy, with no statistical significance between median age and duration of urticaria between males and females. In 11 patients, montelukast had no effect and in 2 patients the urticaria worsened after montelukast was started. 15 patients had peripheral blood basopenia of which 5 patients responded to montelukast. Two patients had positive antinuclear antibody, 3 thyroid peroxidase antibodies and 4 with positive basophil histamine release. All 20 patients who had complement C3 and C4 levels done were within normal limits. Four of 6 patients (67%) with positive specific IgE responded to montelukast and combined anti-H1/H2 therapy. Almost half of our patients with chronic urticaria responded to montelukast and combined anti-H1 and anti-H2 therapy. We were unable to identify any clinical features or laboratory markers that were associated with a response to montelukast. Further studies are required to understand the failure of response of leukotriene inhibition in urticaria.

PMID 22452602  Inflamm Allergy Drug Targets. 2012 Jun;11(3):235-43.
著者: Gabriele Di Lorenzo, Alberto D'Alcamo, Manfredi Rizzo, Maria Stefania Leto-Barone, Claudia Lo Bianco, Vito Ditta, Donatella Politi, Francesco Castello, Ilenia Pepe, Gaetana Di Fede, Giovambattista Rini
雑誌名: J Asthma Allergy. 2008 Dec 9;2:9-16. Epub 2008 Dec 9.
Abstract/Text In vitro and in vivo clinical and experimental data have suggested that leukotrienes play a key role in inflammatory reactions of the skin. Antileukotriene drugs, ie, leukotriene receptor antagonists and synthesis inhibitors, are a class of anti-inflammatory drugs that have shown clinical efficacy in the management of asthma and in rhinitis with asthma. We searched MEDLINE database and carried out a manual search on journals specializing in allergy and dermatology for the use of antileukotriene drugs in urticaria. Montelukast might be effective in chronic urticaria associated with aspirin (ASA) or food additive hypersensitivity or with autoreactivity to intradermal serum injection (ASST) when taken with an antihistamine but not in mild or moderate chronic idiopathic urticaria [urticaria without any possible secondary causes (ie, food additive or ASA and other NSAID hypersensitivity, or ASST)]. Evidence for the effectiveness of zafirlukast and the 5-lipoxygenase inhibitor, zileuton, in chronic urticaria is mainly anecdotal. In addition, there is anecdotal evidence of effectiveness of antileukotrienes in primary cold urticaria, delayed pressure urticaria and dermographism. No evidence exists for other physical urticarias, including cholinergic, solar and aquagenic urticarias, vibratory angioedema, and exercise-induced anaphylaxis.

PMID 21437139  J Asthma Allergy. 2008 Dec 9;2:9-16. Epub 2008 Dec 9.
著者: Nipun Lakshitha de Silva, Hasitha Damayanthi, Anoja Chamarie Rajapakse, Chaturaka Rodrigo, Senaka Rajapakse
雑誌名: Allergy Asthma Clin Immunol. 2014;10(1):24. doi: 10.1186/1710-1492-10-24. Epub 2014 May 7.
Abstract/Text A significant proportion of patients with chronic urticaria respond inadequately to first line treatment with antihistamines. Leukotreine receptor antagonists (LTRA) are also used for chronic urticaria, although firm recommendations on their use are lacking. We performed a systematic review of randomised trials to determine the role of LTRA in treatment of chronic urticaria. A search of PUBMED, EMBASE, SCOPUS, LILACS, the Cochrane Central Register of Controlled Trials, and the Web of Science for relevant randomized control trials or cross over studies yielded 10 eligible studies. The heterogeneity of trials were high, preventing valid meta-analysis of data. Most trials indicated that LTRA are not superior to placebo or antihistamine therapy, while combination therapy of LTRA and antihistamines appear to be more efficacious compared to antihistamine alone. The side effect profile and tolerability of this group of drugs is acceptable. The use of LTRA as monotherapy cannot be recommended. LTRA are effective add-on therapy to anti-histamines, and their use in patients responding poorly to antihistamines is justifiable. Further well designed randomized controlled trials with clear and standardized outcome measures are needed to determine the role of LTRA in chronic urticaria.

PMID 24817895  Allergy Asthma Clin Immunol. 2014;10(1):24. doi: 10.118・・・
著者: Sarah Mitchell, Maria-Magdalena Balp, Miny Samuel, Doreen McBride, Marcus Maurer
雑誌名: Int J Dermatol. 2015 Sep;54(9):1088-104. doi: 10.1111/ijd.12727. Epub 2014 Dec 16.
Abstract/Text BACKGROUND: Patients with chronic spontaneous urticaria (CSU) are sometimes unresponsive to nonsedating, second-generation, H1 antihistamines; this study summarizes published clinical evidence for patients who remain symptomatic despite treatment.
OBJECTIVE: To evaluate, via a systematic literature review, clinical evidence of management strategies for patients with CSU who remain symptomatic despite approved use of nonsedating H1 antihistamines.
METHODS: Using a prespecified protocol, we searched MEDLINE, Embase, the Cochrane Library (1 January 1960-20 December 2011), and published conference abstracts (2010-2012). Rigorous criteria identified trials in patients with CSU who had a history of inadequate response to previous treatment or had used combination treatments. Trials evaluating treatment-naïve patients or first-line therapies were excluded.
RESULTS: Qualitative data synthesized from 26 randomized, controlled trials, four prospective studies, and one retrospective study showed cyclosporine, desloratadine plus dapsone or dipyridamole, montelukast, and omalizumab reduced urticaria activity scores, weals, and pruritus, versus placebo. Optimal treatment doses and durations were unclear due to varying trial durations, outcome measurement scales, and assessment timings. No safety concerns were reported.
CONCLUSIONS: This review confirms that available evidence to guide treatment choice for patients with CSU with inadequate response to H1 antihistamines varies in quality. Further research is warranted due to low-quality trials with methodological and reporting limitations.

© 2014 The International Society of Dermatology.
PMID 25515967  Int J Dermatol. 2015 Sep;54(9):1088-104. doi: 10.1111/i・・・
著者: Jonathan A Bernstein, David M Lang, David A Khan, Timothy Craig, David Dreyfus, Fred Hsieh, Javed Sheikh, David Weldon, Bruce Zuraw, David I Bernstein, Joann Blessing-Moore, Linda Cox, Richard A Nicklas, John Oppenheimer, Jay M Portnoy, Christopher R Randolph, Diane E Schuller, Sheldon L Spector, Stephen A Tilles, Dana Wallace
雑誌名: J Allergy Clin Immunol. 2014 May;133(5):1270-7. doi: 10.1016/j.jaci.2014.02.036.
Abstract/Text These parameters were developed by the Joint Task Force on Practice Parameters (JTFPP), representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, Asthma & Immunology (ACAAI); and the Joint Council of Allergy, Asthma & Immunology. The AAAAI and ACAAI have jointly accepted responsibility for establishing "The diagnosis and management of acute and chronic urticaria: 2014 update." This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the JTFPP, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma & Immunology. The JTFPP understands that the cost of diagnostic tests and therapeutic agents is an important concern that might appropriately influence the work-up and treatment chosen for a given patient. The JTFPP recognizes that the emphasis of our primary recommendations regarding a medication might vary, for example, depending on third-party payer issues and product patent expiration dates. However, because a given test or agent's cost is so widely variable and there is a paucity of pharmacoeconomic data, the JTFPP generally does not consider cost when formulating practice parameter recommendations. In extraordinary circumstances, when the cost/benefit ratio of an intervention is prohibitive, as supported by pharmacoeconomic data, commentary might be provided. These parameters are not designed for use by pharmaceutical companies in drug promotion. The JTFPP is committed to ensuring that the practice parameters are based on the best scientific evidence that is free of commercial bias. To this end, the parameter development process includes multiple layers of rigorous review. These layers include the workgroup convened to draft the parameter, the task force reviewers, and peer review by members of each sponsoring society. Although the task force has the final responsibility for the content of the documents submitted for publication, each reviewer comment will be discussed, and reviewers will receive written responses to comments, when appropriate. To preserve the greatest transparency regarding potential conflicts of interest, all members of the JTFPP and the practice parameter workgroups will complete a standard potential conflict of interest disclosure form, which will be available for external review by the sponsoring organization and any other interested individual. In addition, before confirming the selection of a Work Group chairperson, the Joint Task Force will discuss and resolve all relevant potential conflicts of interest associated with this selection. Finally, all members of parameter workgroups will be provided a written statement regarding the importance of ensuring that the parameter development process is free of commercial bias. Practice parameters are available online at www.jcaai.org and www.allergyparameters.org.

Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
PMID 24766875  J Allergy Clin Immunol. 2014 May;133(5):1270-7. doi: 10・・・
著者: J-J Grob, P Auquier, I Dreyfus, J-P Ortonne
雑誌名: Allergy. 2009 Apr;64(4):605-12. doi: 10.1111/j.1398-9995.2008.01913.x. Epub 2008 Dec 30.
Abstract/Text BACKGROUND: Chronic idiopathic urticaria (CIU) impairs quality of life (QoL). Currently, no consensus exists regarding how second-generation H(1)-antihistamines (proven to control CIU symptoms) should be taken long-term: as daily treatment or only when symptoms return (PRN). We sought to determine which regimen improves or better maintains QoL in CIU: desloratadine (DL) daily or PRN.
METHODS: Subjects with CIU initially responding to DL 5 mg/day for 4 weeks were randomized for an additional 8 weeks, to DL 5 mg/day (arm 1: 'continuous', n = 46) or to DL only on days when urticarial wheals were present (arm 2: "PRN", n = 60). To ensure blinding, treatment was presented in both arms as a combination of daily treatment (arm 1: DL; arm 2: placebo), plus a "rescue" tablet (arm 1: placebo; arm 2: DL) to be taken only in case of symptoms. The main outcome measure was QoL assessed by the VQ-Dermato, a validated French QoL instrument, and the Dermatology Life Quality Index (DLQI).
RESULTS: At 4 and 8 weeks after randomization, subjects taking continuous DL showed statistically significant improvements in VQ-Dermato Global Index score (P = 0.001 and P = 0.016, respectively) and dimension scores for daily living activity, mood state, and social functioning vs subjects taking DL PRN. Improvement in DLQI score at Week 4 was also significantly greater with continuous DL (P = 0.001).
CONCLUSION: Continuous daily therapy with DL 5 mg is a better regimen than PRN treatment to maintain or improve QoL in subjects with CIU.

PMID 19133920  Allergy. 2009 Apr;64(4):605-12. doi: 10.1111/j.1398-999・・・
著者: Karsten Weller, Elena Ardelean, Elisabeth Scholz, Peter Martus, Torsten Zuberbier, Marcus Maurer
雑誌名: Acta Derm Venereol. 2013 Mar 27;93(2):168-74. doi: 10.2340/00015555-1434.
Abstract/Text Non-sedating H1-antihistamines are the recommended first-line treatment for chronic spontaneous urticaria. While efficacy studies usually apply continuous daily treatment regimens, many patients take their medication on demand. In this randomized, double-blind trial we tested whether on-demand H1-antihistamine desloratadine in standard and higher doses is able to improve the resolution of existing wheals. Symptoms of 29 patients with chronic spontaneous urticaria were followed without treatment on one day and again on another day during the next 3 weeks after a single dose of either 5 mg or 20 mg desloratadine, using different objective measures. While the intervention with both doses of desloratadine was effective in terms of a reduction in hyperthermic skin area, there was no improvement in wheal area and wheal volume compared with no treatment. Wheal numbers were reduced after treatment with 20 mg, but not 5 mg, desloratadine. In conclusion, the beneficial effects of non-sedating H1-anti-histamines given on demand appear to be low. Thus, a preventive treatment strategy should be preferred in chronic spontaneous urticaria.

PMID 23053062  Acta Derm Venereol. 2013 Mar 27;93(2):168-74. doi: 10.2・・・

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