Review and Feature Article
How to Approach Chronic Inducible Urticaria

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Chronic inducible urticaria (CIndU) is a group of chronic urticarias characterized by the appearance of recurrent wheals, recurrent angioedema or both, as a response to specific triggers. CIndU includes both physical (symptomatic dermographism, cold and heat urticaria, delayed pressure urticaria, solar urticaria, and vibratory urticaria) and nonphysical urticarias (cholinergic urticaria, contact and aquagenic urticaria). Here, we review the different forms of CIndU with an emphasis on symptomatic dermographism, cold urticaria, cholinergic urticaria, and delayed pressure urticaria. We discuss the clinical features, the diagnostic workup including provocation and threshold testing, and available treatment options.

Section snippets

Pathophysiology of CIndU

The exact pathological mechanisms that result in CIndU are still under investigation. The activation and degranulation of tissue-resident mast cells and the subsequent release of proinflammatory mediators such as histamine play key roles.8, 9, 10, 11 The efficacy of anti-IgE (omalizumab) in many patients with CIndU points to a possible role of IgE in the degranulation of mast cells in CIndU. Type I autoimmunity, also known as autoallergy, is held by many to be of major importance in the

Clinical features

SD (synonym: urticaria factitia, dermographic urticaria) is the most common physical urticaria and characterized by itching and/or burning skin sensations and the development of itchy wheals in response to rubbing, scratching, and/or scrubbing, that is, shearing forces acting on the skin. In very rare cases, angioedema can develop. SD is clinically distinct from the more common “simple” dermographism, where whealing, but no itch sensation, occurs after firm stroking of the skin. White

Clinical features

ColdU (synonym: acquired ColdU or cold contact urticaria) is characterized by the appearance of wheals after contact with cold or cooling and rewarming of the skin (Table II).43, 44, 45, 46 ColdU is the second most frequent subtype of physical urticaria. The annual incidence is 0.05%47 with predominant manifestation in young adults and slightly higher prevalence in women.6 The clinical symptoms occur within minutes after skin contact with cold air, cold liquids, cold solid objects, or

Clinical features

CholU is characterized by itching, redness, and papular whealing induced by exercise and passive warming (eg, hot bath). Emotional stress as well as spicy and hot food can also provoke these symptoms. Typically, these patients show tiny, short-lived wheals with a pronounced flare reaction that is frequently localized to the trunk and extremities83, 84, 85, 86, 87, 88, 89, 90 (Figure 2, G and H) and lasts for 15-60 minutes. But other morphological patterns, including angioedema and systemic

Clinical features

Patients with DPU develop delayed cutaneous erythema and edema with often marked subcutaneous swelling after a pressure stimulus. When this swelling involves the hands or feet, it is indistinguishable from angioedema. Pressure-induced lesions typically occur 4 to 6 hours later, but may occur as early as 30 minutes and last up to 48 hours.110 It is important to note that many patients with DPU also have concomitant CSU and angioedema, and hence many of their lesions may not be exclusively

Outlook and Unmet Needs

Over the past few years, novel tools for the diagnostic workup and new treatment options for patients with SD, ColdU, CholU, and DPU have become available. Less frequent forms of CIndU, however, are still in need of further studies and the development of tools to better manage them in clinical practice.20, 73, 90 Standardized provocation and threshold testing protocols need to be developed for all CIndUs. Their use in diagnosing and monitoring CIndUs helps physicians and patients to understand

References (128)

  • M. Metz et al.

    Omalizumab is effective in cold urticaria-results of a randomized placebo-controlled trial

    J Allergy Clin Immunol

    (2017)
  • Y. Cho et al.

    TRPM8 mediates cold and menthol allergies associated with mast cell activation

    Cell Calcium

    (2010)
  • N. Medic et al.

    Examination of the role of TRPM8 in human mast cell activation and its relevance to the etiology of cold-induced urticaria

    Cell Calcium

    (2011)
  • J. Sanchez et al.

    Prevalence of inducible urticaria in patients with chronic spontaneous urticaria: associated risk factors

    J Allergy Clin Immunol Pract

    (2017)
  • H. Adamski et al.

    Solar urticaria [in French]

    Ann Dermatol Venereol

    (2012)
  • E. Borzova et al.

    Narrowband ultraviolet B phototherapy is beneficial in antihistamine-resistant symptomatic dermographism: a pilot study

    J Am Acad Dermatol

    (2008)
  • A.A. Wanderer

    Essential acquired cold urticaria

    J Allergy Clin Immunol

    (1990)
  • J.P. Dice

    Physical urticaria

    Immunol Allergy Clin North Am

    (2004)
  • H.M. Hoffman et al.

    The role of the inflammasome in patients with autoinflammatory diseases

    J Allergy Clin Immunol

    (2016)
  • C. Gandhi et al.

    Familial atypical cold urticaria: description of a new hereditary disease

    J Allergy Clin Immunol

    (2009)
  • F. Siebenhaar et al.

    Peltier effect-based temperature challenge: an improved method for diagnosing cold urticaria

    J Allergy Clin Immunol

    (2004)
  • M. Metz et al.

    Rupatadine and its effects on symptom control, stimulation time, and temperature thresholds in patients with acquired cold urticaria

    Ann Allergy Asthma Immunol

    (2010)
  • F. Newcombe et al.

    Handedness, speech lateralization and ability

    Neuropsychologia

    (1973)
  • M.E. Weinstein et al.

    Efficacy and tolerability of second- and third-generation antihistamines in the treatment of acquired cold urticaria: a meta-analysis

    Ann Allergy Asthma Immunol

    (2010)
  • F. Siebenhaar et al.

    High-dose desloratadine decreases wheal volume and improves cold provocation thresholds compared with standard-dose treatment in patients with acquired cold urticaria: a randomized, placebo-controlled, crossover study

    J Allergy Clin Immunol

    (2009)
  • J.A. Boyce

    Successful treatment of cold-induced urticaria/anaphylaxis with anti-IgE

    J Allergy Clin Immunol

    (2006)
  • A. Le Moing et al.

    Effective treatment of idiopathic chronic cold urticaria with omalizumab: report of 3 cases

    J Am Acad Dermatol

    (2013)
  • C. Dressler et al.

    Chronic inducible urticaria: a systematic review of treatment options

    J Allergy Clin Immunol

    (2018)
  • P. Bonadonna et al.

    Treatment of acquired cold urticaria with cetirizine and zafirlukast in combination

    J Am Acad Dermatol

    (2003)
  • M. Abajian et al.

    Physical urticarias and cholinergic urticaria

    Immunol Allergy Clin North Am

    (2014)
  • B.M. Czarnetzki

    Ketotifen in cholinergic urticaria

    J Allergy Clin Immunol

    (1990)
  • S. Altrichter et al.

    Development of a standardized pulse-controlled ergometry test for diagnosing and investigating cholinergic urticaria

    J Dermatol Sci

    (2014)
  • K. Koch et al.

    Antihistamine updosing reduces disease activity in patients with difficult-to-treat cholinergic urticaria

    J Allergy Clin Immunol

    (2016)
  • N. Silpa-Archa et al.

    Physical urticaria: prevalence, type and natural course in a tropical country

    J Eur Acad Dermatol Venereol

    (2011)
  • N. Schoepke et al.

    Symptomatic dermographism: an inadequately described disease

    J Eur Acad Dermatol Venereol

    (2015)
  • P.G. van der Valk et al.

    The natural history of chronic urticaria and angioedema in patients visiting a tertiary referral centre

    Br J Dermatol

    (2002)
  • P. Mathelier-Fusade et al.

    Clinical predictive factors of severity in cold urticaria

    Arch Dermatol

    (1998)
  • T.W. Chang et al.

    The potential pharmacologic mechanisms of omalizumab in patients with chronic spontaneous urticaria

    J Allergy Clin Immunol

    (2015)
  • M.K. Church et al.

    The role and relevance of mast cells in urticaria

    Immunol Rev

    (2018)
  • P. Kolkhir et al.

    Autoimmune chronic spontaneous urticaria: what we know and what we don‘t know

    J Allergy Clin Immunol

    (2017)
  • S. Altrichter et al.

    IgE mediated autoallergy against thyroid peroxidase—a novel pathomechanism of chronic spontaneous urticaria?

    PLoS One

    (2011)
  • L. Kring Tannert et al.

    Cold urticaria patients exhibit normal skin levels of functional mast cells and histamine after tolerance induction

    Dermatology

    (2012)
  • M. Kojima et al.

    Solar urticaria. The relationship of photoallergen and action spectrum

    Arch Dermatol

    (1986)
  • H. Miyauchi et al.

    Detection of action, inhibition and augmentation spectra in solar urticaria

    Dermatology

    (1995)
  • M. Sánchez-Borges et al.

    Review of physical urticarias and testing methods

    Curr Allergy Asthma Rep

    (2017)
  • M. Abajian et al.

    Physical urticaria

    Curr Allergy Asthma Rep

    (2012)
  • M. Fleischer et al.

    Physical urticaria [in German]

    Hautarzt

    (2004)
  • T. Zuberbier et al.

    Urticaria: current opinions about etiology, diagnosis and therapy

    Acta Derm Venereol

    (2007)
  • J. Wallengren et al.

    Urticarial dermographism: clinical features and response to psychosocial stress

    Acta Derm Venereol

    (2007)
  • M. Magerl et al.

    Prevention of signs and symptoms of dermographic urticaria by single-dose ebastine 20 mg

    Clin Exp Dermatol

    (2009)
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    No funding was received for this work.

    Conflicts of interest: M. Maurer has received institutional research funding and/or honoraria for consulting/lectures from Allakos, FAES, Genentech, Menarini, MOXIE, Novartis, Sanofi, and Uriach, all outside the current work. J.W. Fluhr declares no conflicts of interest. D.A. Khan has received speaker honoraria from Genentech, outside the current work.

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