Karsten Weller

Unmet clinical needs in chronic spontaneous urticaria. A GA2LEN task force report

To cite this article: Maurer M, Weller K, Bindslev‐Jensen C, Giménez‐Arnau A, Bousquet PJ, Bousquet J, Canonica GW, Church MK, Godse KV, Grattan CEH, Greaves MW, Hide M, Kalogeromitros D, Kaplan AP, Saini SS, Zhu XJ, Zuberbier T. Unmet clinical needs in chronic spontaneous urticaria. A GA2LEN task force report. Allergy 2011; 66: 317–330.

Mast cells promote homeostasis by limiting endothelin-1-induced toxicity

Endothelin-1 (ET-1) is a 21-amino-acid peptide, derived from vascular endothelial cells, with potent vasoconstrictor activity. ET-1 has been implicated in diverse physiological or pathological processes, including the vascular changes associated with sepsis. However, the factors that regulate ET-1-associated toxicity during bacterial infections, or in other settings, are not fully understood. Both the pathology associated with certain allergic and autoimmune disorders, and optimal host defence against bacterial and parasitic infections are mediated by mast cells. In vitro, mast cells can produce ET-1 (ref. 11), undergo ET-1-dependent and endothelin-A receptor (ETA)-dependent activation, and release proteases that degrade ET-1 (ref. 14). Although the potential relationships between mast cells and the ET-1 system thus may be complex, the importance of interactions between ET-1 and mast cells in vivo is obscure. Here we show that ETA-dependent mast-cell activation can diminish both ET-1 levels and ET-1-induced pathology in vivo, and also can contribute to optimal survival during acute bacterial peritonitis. These findings identify a new biological function for mast cells: promotion of homeostasis by limiting the toxicity associated with an endogenous mediator.

Mast cells are required for normal healing of skin wounds in mice

Mast cells (MCs) have recently been reported to play a pivotal role in the elicitation of inflammatory reactions that are beneficial to the host, e.g., during innate immune responses to bacteria. To explore whether MCs also contribute to wound repair, we studied experimentally induced skin wounds in MC‐deficient KitW/KitW‐v mice, normal Kit/ mice, and MC‐reconstituted KitW/KitW‐v mice. Wound closure was significantly impaired in the absence of MCs during the first 6 days of wound healing and histomorphometric analyses of MC degranulation at the wound edges revealed distance‐dependent MC activation, i.e., MC degranulation was most prominent directly adjacent to the wound. In addition, KitW/KitW‐v mice showed impaired extravasation and recruitment of neutrophils to the wounded areas. Notably, wound closure, extravasation, and neutrophil recruitment were found to be normal in MC‐reconstituted KitW/KitW‐v mice. Therefore, we examined whether MCs promote wound healing by releasing histamine or TNF‐. Interestingly, wound closure was reduced in mice treated with an H1‐receptor antagonist but not after treatment with an H2‐receptor antagonist or in the absence of TNF‐. Taken together, our findings indicate that MC activation and histamine release are required for normal cutaneous wound healing.—Weller, K., Foitzik, K., Paus, R., Syska, W., Maurer, M. Mast cells are required for normal healing of skin wounds in mice. FASEB J. 20, E1628 –E1635 (2006)

Anti-Immunoglobulin E Treatment of Patients with Recalcitrant Physical Urticaria

In physical urticaria, exogenous physical factors such as thermal triggers, solar radiation and mechanic triggers including friction or pressure are responsible for the elicitation of symptoms in the skin of patients. Avoidance of the respective stimulus is usually difficult or impossible, and many patients are not sufficiently treated with standard antihistamines. We report that treatment with omalizumab (Xolair®) of 7 patients with physical urticarias [solar urticaria (n = 2), urticaria factitia/symptomatic dermographism (n = 2), cold urticaria, delayed pressure urticaria and localized heat urticaria] resulted in complete symptom control within days after the first injection in 5 patients. In 1 patient, symptoms improved after increasing the dose of omalizumab, and 1 patient with localized heat urticaria did not respond significantly to treatment. Before anti-immunoglobulin E treatment, all patients had suffered from their physical urticaria for years and had had numerous unsuccessful therapies. The overall excellent responses to omalizumab treatment reported here indicate that anti-immunoglobulin E is a safe and effective treatment for recalcitrant physical urticarias.

Development and construct validation of the angioedema quality of life questionnaire

Recurrent angioedema is a frequent clinical problem characterized by unpredictably and rapidly occurring cutaneous and mucosal swellings. These swellings may be painful and/or disfiguring. Upper airway involvement can also lead to dyspnea and suffocation. Although the disease burden is high, there is currently no specific instrument to measure health‐related quality of life (QoL) impairment.

Acquired cold urticaria: clinical picture and update on diagnosis and treatment.

Acquired cold urticaria (ACU) is a frequent subtype of physical urticaria that is caused by the release of proinflammatory mast cell mediators after cold exposure. Although the underlying causes of ACU still remain to be clarified in detail, a wide range of diseases has been reported to be associated with ACU. This review gives an overview of the clinical picture, the differential diagnoses, diagnostic tests and the aetiology of ACU, and summarizes current and novel therapeutic options based on the current literature.

Development, validation, and initial results of the Angioedema Activity Score

Recurrent angioedema (RecA) is a frequent clinical problem characterized by suddenly occurring cutaneous and/or mucosal swellings. Depending on their location, RecA may be painful, hindering, disfiguring, or even life‐threatening. The assessment of disease activity in affected patients is important to guide treatment decisions. Currently, however, there is no standardized and validated outcome measure available to do so.

Efficacy and safety of the interleukin-1 antagonist rilonacept in Schnitzler syndrome: an open-label study

Schnitzler syndrome (SchS) is a rare disease with suspected autoinflammatory background that shares several clinical symptoms, including urticarial rash, fever episodes, arthralgia, and bone and muscle pain with cryopyrin‐associated periodic syndromes (CAPS). Cryopyrin‐associated periodic syndromes respond to treatment with interleukin‐1 antagonists, and single case reports of Schnitzler syndrome have shown improvement following treatment with the interleukin‐1 blocker anakinra. This study evaluated the effects of the interleukin‐1 antagonist rilonacept on the clinical signs and symptoms of SchS.

Interleukin‐31 does not induce immediate itch in atopic dermatitis patients and healthy controls after skin challenge

The most intriguing function attributed to interleukin‐31 (IL‐31) is its ability to induce pruritus in pathologic conditions, such as atopic dermatitis (AD). As of today, this feature of IL‐31 was tested in vivo only in animal models.

High Prevalence of Mental Disorders and Emotional Distress in Patients with Chronic Spontaneous Urticaria.

Quality of life, which is impaired in patients with chronic spontaneous urticaria (CSU), is influenced by comorbid mental disorders. The aim of this study was to assess the prevalence and spectrum of mental disorders and to determine levels of emotional distress in patients with CSU. One hundred patients with CSU were investigated for mental disorders (by specialized diagnostic interviews and psychometric instruments), levels of emotional distress (by the Global Severity Index of the Symptom Check List; SCL-90R GSI) and underlying causes of their urticaria (by dermatological assessment). Forty-eight percent of patients with CSU were diagnosed with one or more psychosomatic disorders; most common were anxiety disorders (especially phobias), followed by depressive and somatoform disorders. The use of psychometric instruments confirmed these findings. Levels of emotional distress were significantly higher and more commonly increased in patients with CSU with mental disorders. In conclusion, patients with CSU frequently experience anxiety, depression, and somatoform disorders, and these disorders are linked to increased emotional distress. These findings call for screening of patients with CSU for mental disorders in routine clinical practice as well as for controlled clinical trials.