These recommendations for the definition, diagnosis and management of chronic inducible urticaria (CIndU) extend, revise and update our previous consensus report on physical urticarias and cholinergic urticaria (Allergy, 2009). The aim of these recommendations is to improve the diagnosis and management of patients with CIndU. Our recommendations acknowledge the latest changes in our understanding of CIndU, and the available therapeutic options, as well as the development of novel diagnostic tools.These recommendations for the definition, diagnosis, and management of chronic inducible urticaria (CIndU) extend, revise, and update our previous consensus report on physical urticarias and cholinergic urticaria (1), a joint initiative of the EAACI (European Academy of Allergology and Clinical Immunology) Dermatology Section, the GA 2 LEN (Global Allergy and Asthma European Network) task force on urticaria, the EDF (European Dermatology Forum), and UNEV (urticaria network e.V.). Changes to the 2009 consensus report reflect the results of studies published since then. Chronic inducible urticariasChronic inducible urticarias (CIndUs) are a subgroup of chronic urticaria, a group of diseases characterized by the recurrence of itchy wheals and/or angioedema for longer than 6 weeks [ Table 1, (2)]. Most CIndUs present with wheals, angioedema, or both. Within the group of CIndU, symptomatic dermographism/urticaria factitia, cold and heat urticarias, delayed pressure urticaria, solar urticaria, and vibratory angioedema are defined as physical urticarias. Nonphysical CIndUs include cholinergic urticaria, contact urticaria, and aquagenic urticaria. CIndUs, in contrast to chronic spontaneous urticaria (CSU), are characterized by the need for specific triggers for wheals, angioedema, or both of these symptoms to develop. Wheals and angioedema in CIndU patients develop only and reproducibly in response to the trigger stimulus that is specific for their condition (e.g., cold exposure in cold urticaria). CIndU signs and symptoms are usually confined to skin areas that are exposed to the Allergy 71 (2016) 780-802

No abstract

BackgroundChronic spontaneous urticaria (csU), which is characterized by recurrent episodes of mast cell-driven wheal and flare-type skin reactions, is often associated with elevated total IgE levels and thyroid autoimmunity. We speculate that some csU patients express IgE autoantibodies against thyroid antigens such as thyroid peroxidase (TPO), which could bind to skin mast cells and induce their activation.MethodsWe developed and used a site-directed human IgE capture ELISA to quantify IgE-anti-TPO. We used this assay and investigated csU patients (n = 478) and healthy control subjects (n = 127) for IgE-anti-TPO and then assessed IgE-anti-TPO-positive and -negative csU patients for clinical and serological differences.Principal FindingsCsU patients were found to express more than 2fold higher IgE-anti-TPO serum levels as compared to healthy control subjects (p<0.001). 54% of csU patients had serum levels higher than the cut off ( = 5 IU/ml). By distribution analyses we identified two distinct subpopulations of csU patients: 1) IgE-anti-TPOlow ( = 39%, IgE-anti-TPO: median 2.17 interquartile range 0.86–5.44,  =  comparable to healthy controls) and 2) IgE-anti-TPOhigh ( = 61%, IgE-anti-TPO: median 6.67, interquartile range 5.39–8.24). IgE-anti-TPO-positive and -negative csU patients had very similar distributions of age and gender as well as disease activity and duration. IgE-anti-TPO-positive csU patients exhibited significantly higher IgG-anti-TPO levels and lymphocyte counts as well as decreased C4 complement levels.ConclusionOur findings show that a sizeable subgroup of csU patients expresses IgE antibodies against thyroid peroxidase. These autoantibodies could cause “autoallergic” mast cell activation, a novel pathomechanism of chronic spontaneous urticaria.

Patients with chronic spontaneous urticaria (CSU) are widely held to often have other autoimmune disorders, including autoimmune thyroid disease. Here, we systematically evaluated the literature on the prevalence of thyroid autoimmunity in CSU and vice versa. There is a strong link between CSU and elevated levels of IgG antithyroid autoantibodies (AAbs), with most of a large number of studies reporting rates of ≥10%. Levels of IgG against thyroid peroxidase (TPO) are more often elevated in CSU than those of other IgG antithyroid AAbs (strong evidence). Levels of IgG antithyroid AAbs are more often elevated in adult patients with CSU than in children (strong evidence). Patients with CSU exhibit significantly higher levels of IgG antithyroid AAbs (strong evidence) and IgE-anti-TPO (weak evidence) than controls. Elevated IgG antithyroid AAbs in CSU are linked to the use of glucocorticoids (weak evidence) but not to disease duration or severity/activity, gender, age, or ASST response (inconsistent evidence). Thyroid dysfunction rates are increased in patients with CSU (strong evidence). Hypothyroidism and Hashimoto's thyroiditis are more common than hyperthyroidism and Graves' disease (strong evidence). Thyroid dysfunction is more common in adult patients with CSU than in children (strong evidence) and in female than in male patients with CSU (weak evidence). Urticaria including CSU is more prevalent in patients with thyroid autoimmunity than in controls (weak evidence). CSU can improve in response to treatment with levothyroxine or other thyroid drugs (strong evidence). Pathogenic mechanisms in CSU patients with thyroid autoimmunity may include IgE against autoantigens, immune complexes, and complement.

No abstract