Chronic urticaria as a systemic disease

Urticaria is one of the most common diseases seen in everyday dermatologic practice, characterized by the development of wheals, angioedema, or both. While acute urticaria is mostly related to allergic or pseudoallergic reaction to food, drugs, or infections, chronic urticaria is a more complex disease with different additional ethiopathologic mechanisms and evoking factors. While urticaria is an undisputed disease of the skin, growing evidence supports, like in other dermatologic diseases, the concept of urticaria as a systemic disease with clinical symptoms and signs predominantly presenting on the skin. In this review, we describe the evidence and association between chronic urticaria and a variety of disorders, such as autoimmune diseases, atopy, infections, metabolic conditions, and neoplastic disorders. Beyond the mechanistic association, the possible common underlying pathomechanisms, such as systemic immunologic processes, are discussed.     

Chronic urticaria

Chronic urticaria (CU) is a disturbing allergic condition of the skin. Although frequently benign, it may sometimes be a red flag sign of a serious internal disease. A multitude of etiologies have been implicated in the causation of CU, including physical, infective, vasculitic, psychological and idiopathic. An autoimmune basis of most of the 'idiopathic' forms is now hypothesized. Histamine released from mast cells is the major effector in pathogenesis and it is clinically characterized by wheals that have a tendency to recur. Laboratory investigations aimed at a specific etiology are not always conclusive, though may be suggestive of an underlying condition. A clinical search for associated systemic disease is strongly advocated under appropriate circumstances. The mainstay of treatment remains H1 antihistaminics. These may be combined with complementary pharmacopeia in the form of H2 blockers, doxepin, nifedipine and leukotriene inhibitors. More radical therapy in the form of immunoglobulins, plasmapheresis and cyclophosphamide may be required for recalcitrant cases. Autologous transfusion and alternative remedies like acupuncture have prospects for future. A stepwise management results in favorable outcomes. An update on CU based on our experience with patients at a tertiary care centre is presented.     

Chronic urticaria

Chronic urticaria has a spectrum of clinical presentations and causes. About 50% of patients with "idiopathic" disease have histamine-releasing autoantibodies in their blood. The term autoimmune urticaria is increasingly being accepted for this subgroup of patients, in whom immunosuppressive therapies may be appropriate if conventional approaches to management are unsuccessful. This article reviews the classification, causes, and management of chronic urticaria in light of recent advances in the understanding of its etiology. LEARNING OBJECTIVE: At the conclusion of this learning activity, participants should have up-to-date knowledge of the classification, assessment, and management of chronic urticaria and understand where the concept of autoimmune urticaria fits into existing frameworks.     

Chronic urticaria is not significantly associated with hepatitis C or hepatitis G infection: a case-control study

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.     

慢性自身免疫性荨麻疹研究进展

慢性自身免疫性荨麻疹发病以自身免疫反应为基础.这类有自身抗体参与的慢性自身免疫性荨麻疹在预后和治疗上均有其特殊性,常规的抗组胺药物治疗很难奏效.研究发现,慢性自身免疫性荨麻疹的发病原因与抗IgE及其受体的自身抗体、自身免疫性甲状腺疾病以及幽门螺杆菌感染、遗传因素、精神因素等诸多因素有关.慢性自身免疫性荨麻疹患者体内B淋巴细胞刺激因子水平增高,刺激产生抗IgE的高亲和力受体抗体和抗IgE抗体,与肥大细胞结合后诱发自身免疫性荨麻疹.     

Most chronic urticaria is food-dependent, and not idiopathic

Abstract: Although chronic urticaria is generally thought to be mostly idiopathic, we have recently provided convincing evidence that in the majority of patients, food ingredients provoke the symptoms and sustain the disease. On a diet largely avoiding preservatives, dyes and natural pseudoallergens, 73% of patients experienced remission of more than 6 months duration, starting within the first 3 weeks after initiation of the diet. This response rate is clearly higher than the reported 24% spontaneous remission rate over the same time period. The specificity of the dietary effect was proven 1) by double-blind provocation with pureed pseudoallergen-low versus -rich food and 2) by induction of a clinical response to a 3-week diet low in pseudoallergens, but not to a standard diabetes diet in 3 patients studied in a double-blind crossover design. On double-blind, placebo controlled oral provocation, only 18% of diet-responsive patients reacted to known food preservatives and dyes, but 71% to pureed tomatoes and 44% to their steem extracts. These findings identify naturally occurring pseudoallergens in food as major elicitors of chronic urticaria. In contrast, autoantibodies against Fc-RIα have been identified in only about 30% of chronic urticaria patients, and evidence for their truly causative role is still lacking since therapeutic measures work in patients irrespective of the presence or absence of the autoantibodies. For both food intolerance and Fc-RIα-autoantibodies in chronic urticaria, the associated pathomechanisms are however still in need of clarification. Meanwhile, the diet-responsiveness in the majority of patients opens new perspectives for the management of chronic urticaria.     

Chronic urticaria is associated with a differential helminth-arthropod-related atopy phenotype

The relationship between atopic sensitization and chronic urticaria is still controversial. In this study, we aimed to compare the prevalence of aeroallergen sensitization in chronic urticaria patients with (CU/As+) and without (CU/As-) sensitization against Anisakis simplex. Forty-nine CU/As+ and 80 CU/As- patients were studied and skin prick tests (SPT) were performed against aeroallergens. We assessed sensitization in a subgroup of patients with allergic rhinoconjunctivitis and/or bronchial asthma (RCBA) and compared the prevalence with a control group of 522 non-urticaria patients with RCBA. Forty-five percent of CU/As- and 60.4% of CU/As+ patients displayed positive SPT to at least one aeroallergen. CU/As+ patients had a higher prevalence of sensitization against pollen, mould or dander (PMD) (52.2% vs 29.1%, P < 0.01), whereas the prevalence of house dust mite (HDM) sensitization was not statistically different (26.3% in CU/As- and 36.7% in CU/As+). However, in chronic urticaria patients with RCBA, 53.8% of CU/As- and 57.9% of CU/As+ patients differed in the prevalence of HDM sensitization compared to the control group (33.5%, P = 0.03), whereas no difference could be stated for PMD sensitization. Compared to RCBA patients, both CU/As+ and CU/As- patients have a higher clinically relevant sensitization rate against HDM, thus displaying a differential atopy phenotype.     

Arachidonic acid transformation is not stimulated in delayed pressure urticaria

Little is known about the molecular mechanisms or inflammatory mediators involved in delayed pressure urticaria (DPU). Pressure sufficient to provoke lesions was applied to the back of six patients with DPU. The levels of products of arachidonic acid transformation in skin exudate from the pressure challenged skin were estimated immediately after pressure was removed and 6 h later when lesions were present. These were compared to levels estimated in a similar way from unchallenged skin in these patients. Levels of leukotriene C4/D4/E4, prostaglandin E2, 12-hydroxyeicosatetraenoic acid and leukotriene B4 were not raised in lesional skin. Our results suggest that arachidonic acid metabolism is not stimulated in DPU.