The Puzzle of Urticaria - International Research Abstracts

By Ram Malkani

Discover the latest edition of International Research Abstracts, filled with over two hundred new insights and developments in the world of urticaria. Dive into the complex world of Chronic Spontaneous Urticaria, where multiple mechanisms may be at play, leading to a puzzle that is waiting to be solved. Explore the intriguing connections between autoimmune reactions, neurotrphins, and metalloproteinase inhibitors, shedding light on the mysterious nature of this condition. Uncover the potential risks and relapses associated with treatments like Omalizumab, and delve into cutting-edge topics such as D-dimer, intradermal tests, and the genetic underpinnings of urticaria. Join us on this journey of discovery and contribute your feedback to unravel The Puzzle of Urticaria.

• Language: English
• Publisher: Ram Malkani
• Release date: Mar 23, 2024
• ISBN: 9798224795390

Ram Malkani

Consultant in Dermatology, in practice, from 1973. Consultant Dermatologist in Jaslok Hospital since 1978. Fellow of the Royal College of Physicians ( Eng) Member of the Indian association of dermatologists, Venereologists and Leprologists Member European Society of Dermatologists and Psychiatrists Member Psychodermatology Association of India Fellow of the American Association of Dermatology Fellow of the European Association of Dermatology Awards and Achievements: Orations ` Psychological approach in Dermatology patients` at the IADVL, Cuticon, 2020. Oration on 'Oculoctaneous Diseases' at the Maharashtra Ophthalmology Association Conference at the Amar Gian Auditorium, Mumbai 1994 Key note address : 'My tryst with Psychodermatology' Delivered at the First National Conference of the Psychodermatology Association of India, held at Kozhikode, Jan 21,2023 Life time achievement awards At the First National Conference of the Psychodermatology Association of India at Kozhikode Jan 21 2023 Life time achievement award -  IADVL, Maharashtra Branch , 2012 at Nanded. Guide - The Premlata award - Best Research for HIV and Drug resistance, at the National IADVL, Pune 2020. A Jaslok Hospital research project. Acievements - President IADVL Maharashtra 1991-92. Convenor HIV prevention programme IADVL, Maharashtra 1996-2008 Founder Member Pychodermatology Association of India, 2019 Research Gate Data - 41 Publications (Researchgate) 3,123 reads 94 citations Immediate Goal Passed my entrance exam for Phd of MUHS in 2020, waiting for a guide. Training Qualified as a Psychodermatologist by the EASDaP and by virtue of 5+ 3 years of 5 days/week Psychoanalysis.

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The Puzzle of Urticaria - International Research Abstracts

Ram Malkani

Published by Ram Malkani, 2024.

While every precaution has been taken in the preparation of this book, the publisher assumes no responsibility for errors or omissions, or for damages resulting from the use of the information contained herein.

THE PUZZLE OF URTICARIA - INTERNATIONAL RESEARCH ABSTRACTS

First edition. March 23, 2024.

Copyright © 2024 Ram Malkani.

Written by Ram Malkani.

The Puzzle of Urticaria

International Research ABSTRACTs

Dr Ram Malkani

Institute of Pscychosomatic Dermatology

Urticaria- First Edition

FOREWORD

Do we understand urticaria? Most Doctors treating Urticaria would like to believe so.

Hives or Urticaria are easy to diagnose because they come and go. Dr Gor- don Sussman of Canada writes, ‘causes of urticarial should be investigated in patients, but most patients will not have an identifiable cause’ (Dermatology news vol 10-Issue 13, 2015, pg4).

At times it could present only as Dermographism (inducible urticarial).Most Doctors panic when it presents as Angioedema with difficulty in swallowing. There is a paranoia about laryngeal oedema and asphyxiation leading to seri- ous consequences. Does it happen at all?

The Non Dermatologists Doctors use cortisone, intravenously, intramuscu- larly, orally indiscriminately. In reality very rarely there is a need to use cor- tisone.

Antihistamines are the mainstay of treatment. Besides antihistaminics in non-responders, there are many innocuous drugs which help, like Doxepin, Terbutaline, Propranol, Leukotriene receptor antagonist (Monteleukast), Tranexamic acid and Danazol (in Angioedema), Omega 3, 6, Nadropirin (low molecular weight heparin), Nifedipine, etc.

Presently the cash rich pharma industry is pushing Omalizumab, by publish- ing favourable results, organising seminars in venues having attractive am- bience and identifying key opinion leaders who are rewarded to continuously brainwash the medical community. The pharma industry is never interested in lavishly promoting an inexpensive drug! If a manufacturer has two antihista- mines, it would only promote the more expensive one.

That is as far as Ethics go.

The simpler way of monitoring Urticaria response to medication, in clinical setting, objectively, is a declining C R Panda Neutrophil/Lymphocyte ratio, as compared to the cumbersome Urticaria Control Test (UCT).

This booklet is a collection of ABSTRACTs for an unbiased understanding of Urticaria.

It is easier to turn the pages of a hard copy, hence the effort.

After reading this ABSTRACT book, hopefully the indiscriminate use of cor- tisone will stop, specially by the non-Dermatologist, medical fraternity.

The Unanswered Questions

Why is Urticaria intermittent? Why does it come and go and come again?

After remission it can relapse. Why relapse after a very long or not so long interval?

What happens to the autoantibodies before it begins and after it goes into re- mission?

How does Autoimmune urticarial respond to antihistamines alone? 5) During an attack of Urticaria, is there any way to know what vasoactive medi- ators are responsible?

6) Urticaria in most cases is short lived. Is this fuss about Quality of life to justify expensive ‘Alternatives’?

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Compiled by

Dr Ram Malkani MD DVD DDV FRCP www.drmalkani.com

Puzzle of Urticaria - Second Edition

FOREWORD

We are glad to present the second addition of International Research AB- STRACTs and given recent advances and research we have added over two hundred new ABSTRACTs in this edition. -

Some of the changes are physical urticaria, which was grouped separate- ly due to the special nature of their eliciting factors, Chronic urticaria has been classified as either Chronic spontaneous urticaria or Chronic Physical urticaria, Chronic idiopathic urticaria (CIU) is replaced by the term Chronic spontaneous urticarial (CSU).

Clinically in a case of Chronic Spontaneous Urticaria, it is not possible to know what mechanism is operating, in a given patient, out of the several possible reasons it is likely that more than one mechanism is operating. For example, in an episode of urticaria, the cause is considered or thought to be due to autoimmune mechanism, all you know could be caused or aggravated by neurotrphins or by inhibitors of metalloproteinase 1.It is also possible that some of the mechanisms are epiphenomenon and not necessarily the cause, like the evidence of increased levels of thromboxane resulting in fibrinolysis.

Omalizumab initially was introduced in the treatment of asthma, subsequent- ly banned, probably because it can at times be responsible for anaphylaxis; there are relapses after Omalizumab treatment just as they are after antish- istamine therapy.

Also newer sections like D-dimer and Urticaria, intradermal tests, urticaria and genetics have been added in this edition.

We will be grateful if you will take some time and provide us your feedback, comments and suggestions on this edition of The Puzzle of Urticaria.

––––––––

Dr. Ram H Malkani MD DVD DDV FRCP Institute of Psychosomatic Dermatology

www.drmalkani.com

26th January 2020

Contents

CHRONIC SPONTANEOUS URTICARIA (CSU)...............9

URTICARIA: CLINICAL COURSE.......................45

URTICARIA : DERMOGRAPHISM.......................61

URTICARIA: ANGIOEDEMA...........................69

URTICARIA : AUTOIMMUNE SYSTEM...................77

URTICARIA: GENETIC STUDIES.......................135

URTICARIA: INTRADERMAL TESTS....................143

URTICARIA: PAEDIATRICS...........................155

URTICARIA: IgE...................................167

URTICARIA: PATHOPHYSIOLOGY.....................177

URTICARIA: D-DIMER..............................207

URTICARIA: PSYCHOLOGICAL ISSUES..................215

URTICARIA : MANAGEMENT.........................233

URTICARIA: ANTIHISTAMINES.......................299

UTICARIA: ALTERNATIVE TREATMENTS...............315

URTICARIA: PSYCHOPHARMACOLOGY.................329

CHRONIC SPONTANEOUS URTICARIA (CSU)

An overview of chronic urticaria.

Beltrani VS

ABSTRACT: Acknowledging urticaria as a symptom of mast cell degranulation is stressed. The biology of the mast cell, and the recognized immunologic and non-immunologic mast cell secretagogues are individually discussed along with mechanisms of activation and mediators released. The major, preformed mediator histamine in the skin produces a prototypic, short-lived urticaria, however, the clinical spectrum and pattern of hives indicate that other mediators contribute to the polymorphism and variable behavior of this symptom. The clinical assessment is almost exclusively restricted to the history and physical examination. Features to review and examine are presented. The cause of acute urticaria is identifi- able (by history) in the majority of patients, and except for hives that accompany an anaphylactic reaction, these patients rarely present to the physician for care. The persistent, or chronic hiver whose history cannot elicit a cause, is rare- ly triggered by an individual trigger, despite extensive professional evaluation. Evidence to support changing the chronological, acute and chronic classi- fication of urticaria to identifiable and non-identifiable triggered urticaria is discussed, as is the futility of extensive, costly laboratory work-ups. The natural history of urticaria reveals that management should be directed toward allowing the patient to maintain an acceptable quality of life (with or without some urticar- ia), until the episode resolves.

Clin Rev Allergy Immunol. 2002 Oct;23(2):147-69.

Chronic Idiopathic Urticaria

Malcolm W Greaves

ABSTRACT: Chronic idiopathic urticaria has long been a demoralizing disease, baffling allergists and dermatologists alike, to the detriment of the patient. Recent findings, however, have shed light on causation in many, though not all, of these patients. The purpose of this review is to bring the reader up to date on the current position regarding aetiology and pathogenesis and the strength of the evidence. The review also seeks to point up rational approaches to diagnosis and treatment in the light of these developments. Chronic idiopathic urticaria encompasses at least two subgroups. One of these is the now well-established entity of autoim- mune chronic urticaria, due to autoantibodies against either the high-affinity IgE receptor Fc epsilon R1 or, less commonly, IgE. These patients, who co-segregate with chronic idiopathic urticaria patients having an increased frequency of anti- thyroid autoantibodies, represent 30-50% of the patients previously designated as having chronic idiopathic urticaria. Convenient routine diagnostic tests for this subset remain elusive. The remaining 50% of patients with chronic idiopathic urticaria remain truly ‘idiopathic’, although the condition in some may have an autoimmune basis, autoantibodies having eluded current techniques for detection. Selected patients with autoimmune urticaria may benefit from immunotherapy. It is now known that in 30-50% of patients with chronic idiopathic urticaria, the

condition has an autoimmune basis, although confirmation of the diagnosis in these patients is not straightforward. In selected patients, attempts to establish this diagnosis are worthwhile since there are important therapeutic implications. Current Opinion in Allergy and Clinical Immunology 11/2003; 3(5):363-8

Epidemiology of Chronic Urticaria in Korea Using the Korean Health Insurance Database, 2010-2014

Nami Lee · Jeong-Dong Lee · Hyun-Young Lee · Young-Min Ye

ABSTRACT: Purpose: There are very few epidemiological studies on chronic urticaria (CU). We aimed to investigate the prevalence of CU and to depict demographics and medication patterns for the disease in a nationwide population- based study.

Methods: Data on urticaria (L50 of the International Classification of Diseases, 10th revision) from 2010 to 2014 were obtained from the Korean Health Insur- ance Review and Assessment Service. Algorithms designed to evaluate prescrip- tion drug claims for antihistamines were applied to identify CU.

Results: The crude prevalence of CU was 2,256.5 per 100,000 person-years and tended to increase every year. The age-standardized prevalence of CU was sig- nificantly higher in females than in males (2,466.8 vs 1,819.2 per 100,000 per- son-years, P < 0.001). Age-specific prevalence was highest for older adults over the age of 65 years and lowest for ages 10-29 years. The median duration of CU was 591 days, and symptoms lasted for at least 1 year in 61.9% of patients. Gas- trointestinal disease was the most common comorbidity in adults, whereas aller- gic rhinitis and common cold were more prevalent in children with CU. Around a third of CU patients were taking antihistamine treatment alone, and 70% were treated with both antihistamines and systemic corticosteroids. Cyclosporine was prescribed for 0.02% of CU patients.

Conclusions: The present study outlines recent longitudinal epidemiological data on the prevalence of CU in Korea. In light of limitations on the use of claims data, including no specific disease code for CU and a possible discordance between drug claims and the presence of urticaria symptoms, further investigations are necessary to describe the exact epidemiologic profile of CU patients.

The Korean Academy of Asthma, Allergy and Clinical Immunology.

Full-text available · Article · Jan 2017 · Allergy, asthma &

Computer-assisted Medical Decision-making System for Diagnosis of Urticaria

Jabez J. Christopher · Harichandran Khanna Nehemiah · Kannan Arputharaj

· George L. Moses

ABSTRACT: Background: Urticaria is a common allergic disease that affects all age groups. Allergic disorders are diagnosed at allergy testing centers using skin tests. Though skin tests are the gold standard tests for allergy diagnosis, specialists are required to interpret the observations and test results. Hence, a computer-as-

sisted medical decision-making (CMD) system can be used as an aid for decision

support, by junior clinicians, in order to diagnose the presence of urticaria. Methods: The data from intradermal skin test results of 778 patients, who exhib- ited allergic symptoms, are considered for this study. Based on food habits and the history of a patient, 40 relevant allergens are tested. Allergen extracts are used for skin test. Ten independent runs of 10-fold cross-validation are used to train the system. The performance of the CMD system is evaluated using a set of test sam- ples. The test samples were also presented to the junior clinicians at the allergy testing center to diagnose the presence or absence of urticaria.

Results: From a set of 91 features, a subset of 41 relevant features is chosen based on the relevance score of the feature selection algorithm. The Bayes classification approach achieves a classification accuracy of 96.92% over the test samples. The junior clinicians were able to classify the test samples with an average accuracy of 75.68%.

Conclusion: A probabilistic classification approach is used for identifying the presence or absence of urticaria based on intradermal skin test results. In the ab- sence of an allergy specialist, the CDM system assists junior clinicians in clinical decision making.

Full-text available · Article · Nov 2016

Etiology and Treatment of Chronic Urticaria

Young Koo Jee

ABSTRACT: Chronic urticaria is a well-known disease entity, characterized by the rapid appearance of frequently occurring, short-lived wheals, surrounded by a bright-red flare, and often accompanied by angioedema. Any pattern of recur- rent urticaria occurring at least twice a week for 6 weeks is called chronic. The cause of chronic urticaria is undefined and its diagnosis requires exclusion of other conditions with somewhat similar symptoms. Degranulation of mast cells with release of histamine is central to the development of wheals. About 26~50% of patients with idiopathic urticaria have histamine-releasing autoantibodies in their blood. Urticaria has a profound impact on the quality of life. It is essential to avoid substances likely to trigger or intensify episodes. Treatment is directed at eliminating or at least substantially reducing symptoms. The most important pharmacotherapy is non-sedating H1 antihistamines. They have proved to be ef- fective in double-blind controlled studies. However, alternative therapies may be required because of different urticaria subtypes and individual variations. Immu- nosuppressive drugs such as cyclosporin A and corticosteroids should not be used as a long-term management due to undesirable side effects.

Aug 2004 • Taehan Ŭihak Hyŏphoe chi. The Journal of the Korean Medical

Association

Chronic Idiopathic Urticaria: Systemic Complaints and Their Relation- ship with Disease and Immune Measures

Judy C. Doong • Kris Chichester • Eric T. Oliver • Sarbjit S. Saini

ABSTRACT: Background: Patients with chronic idiopathic urticaria (CIU)/ chronic spontaneous urticaria sometimes report systemic complaints (SCs). Ob- jective: We sought to determine the frequency and characteristics of SCs among patients with CIU, as well as the association of SCs with disease measures, baso- phil histamine release, and serum tryptase.

Methods: Adult patients with CIU were recruited from a university allergy clinic. Patients completed a disease symptom survey and underwent blood sampling for subsequent basophil histamine release and serum tryptase measurement.

Results: A total of 155 patients with CIU were surveyed, with 103 reporting SCs with concomitant hives as follows: joint pain or swelling (55.3%), headache/fa- tigue (47.6%), flushing (42.7%), wheezing (30.1%), gastrointestinal complaints (26.2%), and palpitations (9.7%). Patients with SCs (CIU-SC) were compared with those with no SCs (CIU-NSC). Both groups had similar demographic char- acteristics (average age in 40s, majority female and white) and basophil hista- mine release profiles. CIU-SC had significantly greater disease duration (51.5% CIU-SC vs 30.8% CIU-NSC had >4 years duration), emergency department visits (41.7% vs 23.1% had >1 visit in the last year), CIU-related work absences (65% vs 27.5% had >1 day), oral corticosteroid use (84.5% vs 59.6%), quality-of-life impairment (76.1 vs 59.2 SkinDex score), and serum tryptase levels (5.1 ng/mL vs 3.9 ng/mL).

Conclusions: Despite similar demographic characteristics and basophil profiles as patients with CIU-NSC, patients with CIU-SC have features of greater disease burden (work absences, emergency department visits, and corticosteroid use), quality-of-life impairment, and baseline serum tryptase levels. http://onlinelibrary.wiley.com/doi/10.1111/all.12313/

Guideline for the definition, classification, diagnosis, and management

of urticaria: the 2013 revision and update.

Zuberbier T1, Aberer W, Asero R, Bindslev-Jensen C et al

ABSTRACT: This guideline is the result of a systematic literature review using the ‘Grading of Recommendations Assessment, Development and Evaluation’ (GRADE) methodology and a structured consensus conference held on 28 and 29 November 2012, in Berlin. It is a joint initiative of the Dermatology Section of the European Academy of Allergy and Clinical Immunology (EAACI), the EU-funded network of excellence, the Global Allergy and Asthma European Net- work (GA(2) LEN), the European Dermatology Forum (EDF), and the World Allergy Organization (WAO) with the participation of delegates of 21 nation- al and international societies. Urticaria is a frequent, mast cell-driven disease, presenting with wheals, angioedema, or both. The life-time prevalence for acute urticaria is approximately 20%. Chronic spontaneous urticaria and other chronic

forms of urticaria do not only cause a decrease in quality of life, but also affect performance at work and school and, as such, are members of the group of severe allergic diseases. This guideline covers the definition and classification of urti- caria, 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. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS).

Allergy. 2014 Jul;69(7):868-87. doi: 10.1111/all.12313. Epub 2014 Apr 30.

How to assess disease activity in patients with chronic urticaria?

A. Młynek, A. Zalewska-Janowska, P. Martus, P. Staubach, T. Zuberbier, M.

Maurer

ABSTRACT: The current EAACI/GA²LEN/EDF guidelines recommend assess- ing disease activity in chronic urticaria (CU) by using an established and well-de- fined symptom score, i.e. the urticaria activity score (UAS), which combines daily wheal numbers and pruritus intensity. However, this UAS has never been formally tested for its suitability in assessing CU activity.

Aim: To determine the UAS correlation with quality of life (QoL) in CU patients

and to compare the UAS to other symptom scores.

Methods: Chronic urticaria symptoms (wheals, erythema, angioedema, pruritus) were assessed on seven consecutive days in 111 CU patients for their numbers, duration, size, and/or intensity. Quality of life was assessed by using the Der- matology Life Quality Index. Both, urticaria activity and QoL were determined before and after a 3-week period, in which the patients followed a pseudoaller- gen-low diet.

Results: Urticaria activity score values correlated positively, albeit weakly, with QoL impairment in CU patients (r2 = 0.31, P < 0.05). Also, changes in QoL fol- lowing a pseudoallergen-low diet were reflected by the changes observed in the UAS (r2 = 0.30, P < 0.05). No significant differences were found comparing the QoL correlation of the UAS and other symptom scores combining up to four CU symptom qualities. Quality of life correlation with UAS values increased with the number of days the UAS was assessed and plateaued starting from the fourth consecutive day.

Conclusions: Our findings back the current guideline recommendations to use the UAS for monitoring disease activity in CU patients. Urticaria activity score mean values of at least four consecutive days should be used.

DOI: 10.1111/j.1398-9995.2008.01726.

F1000 Research Analysis of Disease Activity Categories in Chronic Spontaneous/Idiopathic Urticaria

D. Stull • D. McBride • H. Tian • C. Grattan

ABSTRACT: Measurement of disease activity guides treatment of chronic spon- taneous urticaria (CSU). A weekly Urticaria Activity Score―here, the average of twice-daily patient assessment of itch and hives scores summed over 1 week (UAS7TD) ―measures severity from 0 to 42. Insufficient evidence exists wheth- er disease activity states, defined by categorical UAS7TD scores, correlate with other patient-reported outcomes and treatment response. To evaluate and compare categorical UAS7TD scores with selected measures of disease-related quality of life and impact. Data from three randomised clinical trials of Omalizumab in CSU were pooled. Continuous UAS7TD scores were categorised into five disease ac- tivity states: urticaria-free, well-controlled, mild, moderate, and severe urticar- ia. Total scores from the Dermatology Life Quality Index (DLQI); the Chronic Urticaria Quality of Life questionnaire (CU-Q2oL); and questions on sleep and daily activity interference, presence of angioedema, and diphenhydramine use were compared within categorised UAS7TD disease-state scores, using one-way analyses of variance for analysis at different time points and mixed-effects re- gressions for analysis of all data pooled. Pooled analyses showed that categorical UAS7TD disease states accurately predicted differences among treated CSU pa- tients with different levels of disease activity. A consistent pattern existed between categories, with higher-activity disease states associated with significantly higher impact and an increase in angioedema frequency. Results at different treatment time points were consistent. Categorical UAS7TD disease states can discriminate between measures when considering the impact of urticaria activity. Using five categorical disease states could simplify clinical assessment and monitoring of treatment efficacy.

Mar 2017 • British Journal of Dermatology

Analysis of primary treatment and prognosis of spontaneous urticaria

Toshihiko Tanaka • Makiko Hiragun • Michihiro Hide • Takaaki Hiragun

ABSTRACT

Background: The prognosis of spontaneous urticaria in association with early treatment remains unclear. In this study, we retrospectively studied the prognosis of acute spontaneous urticaria in relation to age and treatments in a local clinic of dermatology.

Methods: Out of 5000 patients who visited an office dermatology clinic, clinical records of patients with spontaneous urticaria were extracted. Their prognosis and the relation to age and treatments were analysed by the Kaplan-Meier method and generalized Wilcoxon test.

Results: Among 386 patients diagnosed with spontaneous urticaria, 284 patients (73.6%) began treatments within a week after the onset. Their non-remission rates after one week, four weeks and one year from the onset were 26.8%, 15.0% and

6.7%, respectively. The non-remission rates of patients who were 20-years-old or younger by one year after the onset of urticaria, were significantly lower than those of patients older than 20-years-old. No apparent relationship between remis- sion rates and sex or the use of steroids was detected. However, the non-remission rates of urticaria treated with a standard dose of antihistamine were lower than that treated with additional medications.

Conclusions: Most patients who began treatments within one week from the onset remitted quickly. However approximately 7% of them continued to suffer from symptoms for more than a year. Such prolongation tended to be seen among patients who required other medications in addition to a standard dose of antihis- tamine.

Jan 2017 • Allergology International

https://www.researchgate.net/publication/312391126_Analysis_of_primary_  treatment_and_prognosis_of_spontaneous_urticaria.

Serum C - reactive protein, Neutrophil-Lymphocyte Ratio and Uric Acid Levels in Chronic Spontaneous Urticaria

Ezgi Aktaş Karabay • Aslı Aksu Çerman • İlknur Kivanç Ltunay

ABSTRACT: Objective: Recent studies implicate the role of inflammatory re- sponses in chronic spontaneous urticaria (CSU). The purpose of this study was to analyse the levels of neutrophil-lymphocyte ratio (NLR), serum C-reactive pro- tein (CRP) and uric acid levels in CSU patients, and to investigate the relationship between these inflammatory parameters and disease activity.

Material and Methods: A total of 100 people, consisting of 50 chronic urticaria patients and 50 healthy controls, who have no systemic disease, inflammatory, infectious or autoimmune disease, malignancy, were included in the study.

Results: NLR and serum CRP levels were significantly higher in patients with CSU than in healthy controls (p< 0.001, p< 0.001, respectively). The levels of uric acid did not show a statistically significant difference between CSU patients and controls (p= 0.359). A significant positive correlation was found between NLR and CRP in patients with CSU (p= 0.001, r= 0.442).When CSU patients were evaluated according to disease severity, serum CRP levels were significantly higher in patients with severe CSU than in patients with mild-moderate CSU (p= 0.038).

Conclusion: Several biomarkers have been studied in systemic diseases to deter- mine the inflammatory process ongoing and the relationship between these mark- ers and disease activity has been investigated. It can be concluded that CRP and NLR can be used to assess the inflammatory status in CSU and may be useful parameters during the follow-up of these patients. It is known that NLR and CRP are diagnostic and prognostic markers of cardiovascular diseases. Elevated values of NLR and CRP may demand caution regarding cardiovascular comorbidities that may accompany chronic urticaria.

Dec 2016 • Turkiye Klinikleri Dermatoloji

CRP relevance in clinical assessment of chronic spontaneous urticaria Tunisian patients

Amal Maouia • Monia Youssef • Nadia Leban • Asma Kassab

ABSTRACT: Background: Chronic spontaneous urticaria (CSU) is a common dermatological condition defined by the sudden occurrence of daily wheals and pruritus for at least 6 weeks. Multifactorial origin is suggested such as Oxidative stress. This latter may play a double role as a trigger and remnant agent. Objec- tives: The first aim of this study is to investigate antioxidant status, inflammatory proteins, hematologic counts and clinical assessment in CSU patients. The second aim is to evaluate the effect of a first-line treatment: Desloratadine 5mg/day on these different parameters.

Patients and Methods: This study enrolled 30 CSU patients and same number of controls. We assessed the Urticaria Activity Score (UAS), Total antioxidant status (TAS), glutathione S-Transferase (GST), Superoxide dismutase (SOD), glutathi- one peroxidase (GPx), Catalase (CAT), Albumin, Alpha 1, alpha2, beta1 beta2, gamma globulins, CRP and hematologic numeration.

Results: At baseline Alpha1, alpha2, beta1, beta2, gamma globulins, CRP, SOD activity, leukocytes and basophils were significantly higher in patients versus con- trols (p < 0.05). TAS, GST, CAT, GPx and albumin were significantly low in patients versus controls (p < 0.05). After treatment, TAS, GST and GPx were sig- nificantly increased in patients versus patients before treatment (p < 0.001). SOD, alpha1, alpha2, beta1, beta2, gamma globulins, CR\P, albumin, leukocytes and basophils were significantly decreased after treatment versus before treatment (p

< 0.05). A significant correlation between CRP and UAS (r = 0.3; p = 0.011) was noted. UAS assessment revealed the efficacy of 30 days-antihistaminic treatment. Conclusion: Desloratadine exerted anti-inflammatory and antioxidant effects on CSU patients revealed by CRP. Patients’ remission was synergistic to CRP atten- uation emphasizing CRP relevance for CSU clinical assessment.

Mar 2017 • Cutaneous and Ocular Toxicology

Unmet clinical needs in chronic spontaneous urticaria. A GA (2) LEN Task Force report

M. Maurer • K. Weller • C. Bindslev-Jensen • T. Zuberbier

ABSTRACT:. Chronic spontaneous urticaria, formerly also known as chronic idiopathic urticaria and chronic urticaria (CU), is more common than previously thought. At any time, 0.5–1% of the population suffers from the disease (point prevalence). Although all age groups can be affected, the peak incidence is seen between 20 and 40 years of age. The duration of the disease is generally 1–5 years but is likely to be longer in more severe cases, cases with concurrent angioedema, in combination with physical urticaria or with a positive autologous serum skin test (autoreactivity).

Chronic spontaneous urticaria has major detrimental effects on quality of life, with sleep deprivation and psychiatric comorbidity being frequent. It also has a

large impact on society in terms of direct and indirect health care costs as well as reduced performance at work and in private life. In the majority of patients, an underlying cause cannot be identified making a causal and/or curative treatment difficult. Non sedating H1-antihistamines are the mainstay of symptomatic therapy, but treatment with licensed doses relieves symptoms effectively in <50% of patients. Although guideline-recommended updosing up to fourfold increases symptom control in many patients, a substantial number of patients have only little benefit from H1-antihistamines. Consequently, there is a great need for new therapeutic strategies.

Mar 2011 • Allergy 2011; 66: 317–330.

Impact of chronic urticaria on the quality of life of patients followed up at a university hospital

Gabriela Andrade Coelho Dias • Gisele Viana Pires • et al

Background Chronic urticaria is a debilitating disease that considerably affects health-related quality of life, and the Chronic Urticaria Quality of Life Question- naire is the only questionnaire specifically designed for its evaluation.

Objective To evaluate the quality of life of patients with chronic urticaria, using the Brazilian Portuguese version of the Chronic Urticaria Quality of Life Ques- tionnaire.

Methods The Chronic Urticaria Quality of Life Questionnaire was self-adminis- tered in 112 chronic urticaria patients and disease activity was assessed through the Urticaria Activity Score. Clinical and socio-demographic characteristics of patients were studied, such as: age, sex, etiologic diagnosis of chronic urticaria, duration of disease and Urticaria Activity Score.

Results The population studied was composed 85.72% of women with a mean age of 46 years (18-90), while the median disease duration period was 10 years (3 months-60 years). Regarding the etiologic diagnosis, 48.22% had chronic spontaneous urticaria; 22.32% associated with inducible urticaria, 28.57% with chronic autoimmune urticaria, and 23.21% had physical urticaria alone. Disease activity evaluated using the Urticaria Activity Score was 1.04 ± 1.61 (0-6). The total score for the Chronic Urticaria Quality of Life Questionnaire was 36 (0-100) and dimension I (sleep/mental status/eating) had a greater impact on quality of life. The items with the highest mean scores were nervousness and shame over lesions, while the items with the lowest scores were lip swelling and limitations on sporting activities.

Conclusions Chronic urticaria compromises patients’ quality of life, mainly those with more severe disease or who are diagnosed with chronic autoimmune urti- caria.

Dec 2016 • Anais Brasileiros de Dermatologia

Urticaria and Angioedema: an Update on Classification and Pathogen- esis

Susanne Radonjic-Hoesli • Kathrin Scherer Hofmeier • Sara Micaletto et al

ABSTRACT: Urticaria is a common, mast cell-driven disease presenting with wheals or angioedema or both. In the last years, urticaria has increasingly attract- ed notice to clinicians and researchers, last but not least inspired by the approval of Omalizumab, an anti-IgE antibody, for urticaria treatment. There is wide con- sensus on the clinical classification based on duration and elicitation. However, the pathogenesis is incompletely understood. This review summarizes current guidelines for the management and novel insights in the pathogenesis of urticaria with special focus on their impact on clinical praxis. The classification of urticaria subgroups is mainly based on clinical criteria: acute and chronic urticaria (CU). Chronic urticaria comprises both chronic spontaneous urticaria (CSU) and chron- ic inducible urticaria (CIndU) that includes physical and non-physical urticarias. Recent research focused on characterizing the role of cells and mediators involved in the pathogenesis of urticaria, identifying the mechanisms of mast cell activa- tion, and investigating underlying autoimmune processes in chronic spontaneous urticarial. Currently, non-sedating antihistamines and Omalizumab, an antiimmu- noglobulin E antibody, are recommended for the therapy of chronic urticaria, as both exhibit a favorable efficacy and safety profile. Novel therapeutic strategies aim at specifically targeting cells and mediators involved in the pathogenesis of urticaria.

Jul 2017 • Clinical Reviews in Allergy & Immunology

Physical Urticaria

Marina Abajian • Agnieszka Młynek • Marcus Maurer

ABSTRACT: The physical urticarias are a heterogeneous subgroup of chronic urticarias in which wheals can be reproducibly induced by different specific phys- ical stimuli such as cold, heat, pressure, vibration, or sunlight. Physical urticarias comprise up to 25 % of chronic urticarias and occur more frequently in young adults. Symptoms, i.e. wheal and flare responses or angioedema, are usually lim- ited to the skin areas exposed to the eliciting stimulus. However, generalised ur- ticaria with variable extracutaneous manifestations can also occur. Some patients may also present with more than one physical urticaria. Skin lesions in physical urticaria result from mast cell activation and mediator release. The mechanisms by which physical stimuli activate skin mast cells are not fully understood. Be- cause of this, trigger avoidance and symptomatic treatment are key therapeutic concepts for physical urticarias. Identification of the inducing physical trigger, including its individual thresholds, is necessary for an effective therapy. Here, we have summarized clinical features, diagnostic workup and therapy options for physical urticarias.

Jun 2012 • Current Allergy and Asthma Reports

Advances in Understanding and Managing Chronic Urticaria

Gordon Sussman • Yasmin Moolani • Charles Lynde

ABSTRACT: There have been recent advances in the classification and man- agement of chronic urticaria. The new term chronic spontaneous urticaria (CSU) has replaced chronic idiopathic urticaria and chronic autoimmune urticaria. In addition, chronic inducible urticaria (CINDU) has replaced physical urticaria and includes other forms of inducible urticaria, such as cholinergic and aquagenic urticaria. Furthermore, novel research has resulted in a new understanding with guidelines being revised in the past year by both the American Academy of Al- lergy, Asthma, and Immunology (AAAAI) and the European Academy of Allergy and Clinical Immunology (EAACI)/Global Allergy and Asthma European Net- work (GA (2)LEN)/European Dermatology Forum (EDF)/World Allergy Organi- zation (WAO). There are some differences in the recommendations, which will be discussed, but the core updates are common to both groups. The basic treatment for chronic urticaria involves second-generation non-sedating non-impairing H 1 antihistamines as first-line treatment. This is followed by up to a 4-fold increase in the licensed dose of these H 1 antihistamines. The major therapeutic advance in recent years has been in third-line treatment with Omalizumab, a humanized monoclonal anti-immunoglobulin E (anti-IgE) antibody that prevents binding of IgE to the high-affinity IgE receptor. Several multicenter randomized controlled trials have shown safety and efficacy of Omalizumab for CSU. There are also some small studies showing efficacy of Omalizumab in CINDU. While there were previously many treatment options which were lacking in strong evidence, we are moving into an era where the treatment algorithm for chronic urticaria is simpli- fied and contains more evidence-based, effective, and less toxic treatment options. Feb 2016 • F1000 Research

Evaluation of Etiological Factors in Patients with Chronic Urticaria

Emine Colgecen • Kemal Ozyurt • Ali Irfan Gul • Serap Utas

ABSTRACT: In the last few decades, increasing understanding of the patho- mechanisms involved in chronic urticaria has highlighted the heterogeneity of different subtypes, and chronic urticaria is now classified as chronic spontaneous urticaria and inducible urticaria. Although many factors are thought to be in- volved in chronic urticaria, the etiology is yet to be clarified. The purpose of this study was to investigate etiological factors in patients with chronic urticaria. Five hundred patients with chronic urticaria, 351 women and 149 men, were studied for etiological factors. The autologous serum skin test was performed on 197 pa- tients. Provocation testing for physical urticaria was performed on 354 patients. Patients with acute urticaria were excluded from the study. We determined at least one focus of infection that might be involved in the etiology of the disease in 18.8% of cases. Patients with infections were treated, and symptoms resolved after treatment in six cases (5.3%). Autologous serum skin tests were positive in 125 patients (63.5%).

Apr 2015

Acute-phase response in chronic urticaria

Kasperska-Zajac

ABSTRACT: The patterns of acute-phase response (APR) biomarkers differ upon various inflammatory conditions. Little information is available on the sys- temic inflammatory response in urticaria ⁄ angio-oedema. It has been shown that concentrations of circulating APR biomarkers, IL-6 and C-reactive protein (CRP), are elevated more in severe chronic urticaria (CU) than in patients showing milder urticarial symptoms. It is not clear whether the increase of IL-6and CRP is merely an epiphenomenon or may contribute to the pathogenesis of CU. It is tempting to speculate that mediators of APR may enhance urticarial inflammation. In ad- dition, there is some association between APR and activation of coagulation ⁄ fibrinolysis in CU. It is well known that even slight elevation in CRP baseline concentrations enough to produce significant increase in cardiovascular risk. In this light, one should ask whether CU patients, in particular those showing stron- ger systemic inflammatory response and long-lasting course are more vulnerable