Management of idiopathic urticaria with H1 + H2 antagonists. A crossover double blind long-term study

A randomized crossover double-blind study in a selected group of patients with idiopathic urticaria (15 patients; 10 females, 5 males; 20-80 years old) has been performed in order to examine the clinical efficacy of H1 + H2-antagonists in this disease, as compared with the H1-antagonist alone and with placebo. Chlorpheniramine (4 X 4 mg/d) and cimetidine (4 X 400 mg/d) were administered, each of them over 4 weeks, after one week wash-out period. The number of wheals, the time of their persistance as well as the presence of itching were daily registered and then evaluated. The entire group showed no difference between antihistamines and placebo. Nevertheless, 4 patients have registered a definitely better response to the H1-antagonist, 4 other patients responded distinctly better to the combined H1 + H2-treatment and 5 patients showed no preference at all. In a long-term follow up period of 3 months the effect of chlorpheniramine became even better, whereas the response to the combined treatment remained unchanged. It seems that the clinical efficacy of H1 + H2-antagonists is rather moderate in idiopathic urticaria. Nevertheless, in individual cases non-responding to H1-antagonist the combined administration of H1 + H2-antagonists may be more beneficial for the patient.     

Comparison of chronic autoimmune urticaria with chronic idiopathic urticaria

BACKGROUND: Chronic urticaria has been described in patients with Helicobacter pylori infection. Despite numerous studies, the correlation between H. pylori infection and chronic urticaria is doubtful. Our study was performed to determine the prevalence of H. pylori infection in autoimmune urticaria and in patients suffering from autoimmune urticaria and autoimmune thyroiditis. METHODS: The authors widely investigated 48 patients. The examinations were extended principally to autologous serum skin test, antithyroid antibodies, and the presence of H. pylori infection as well as detection of antibodies against H. pylori. RESULTS: Out of the 48 patients, 26 were regarded as having autoimmune origin. The prevalence of antithyroid antibodies was different in the two groups of patients with urticaria. There were 11 patients (42.3%) in the autoimmune group compared with three patients (13.6%) in the nonautoimmune group with antithyroid peroxidase antibody (P = 0.03). The difference in the prevalence of H. pylori infection was significant between autoimmune urticaria with and without thyroid autoimmunity (90.9% vs. 46.7%; P = 0.02). Autoimmune thyroiditis was connected with CagA +H. pylori strains, as the H. pylori- specific IgG antibodies revealed significant differences in a prevalence of 120 kDa (P < 0.05). CONCLUSIONS: The authors observed a relationship between autoimmune urticaria and autoimmune thyroiditis. The results strengthen the possibility of cross-reactivity being triggered between CagA plus H. pylori strains and some other organ-specific autoimmune diseases such as autoimmune urticaria and autoimmune thyroiditis. This indicates a possible role of H. pylori in triggering autoimmune urticaria in at least a select group of patients.     

Review of H1 antihistamines in the treatment of chronic idiopathic urticaria

Chronic idiopathic urticaria (CIU) can have a profound effect on patient quality of life (QOL). Ideally, any therapy used to treat CIU should be effective across a wide range of doses without causing unwanted side effects; a wide therapeutic window allows the physician to tailor treatment to the individual. Oral H1 antihistamines are the mainstay of therapy for CIU, but agents within this class diverge in their individual therapeutic indices. The literature was reviewed to compare the currently available oral H1 antihistamines regarding their efficacy and safety at a wide range of doses. If sedation and cognitive impairment are considered relevant to treatment selection due to their effect on QOL and safety, then newer-generation agents should be selected over older-generation antihistamines. There are few well-controlled clinical studies in which newer-generation agents have been directly compared. Moreover, there are no evidence-based data demonstrating statistical superiority of one newer-generation agent over another in the treatment of CIU. However, of the newer agents, those that are labelled nonsedating at recommended doses (fexofenadine, loratadine, and desloratadine) should be selected over cetirizine. In cases where the physician judges that a higher-than-recommended dose should be prescribed, or when the patient is likely to take a higher dose, the relative safety profile of these agents demands detailed consideration.     

慢性特发性荨麻疹免疫机制研究进展

慢性特发性荨麻疹的病因目前尚不明确。研究表明,慢性特发性荨麻疹发病大多有自身免疫机制参与,现已发现了数种与慢性特发性荨麻疹有关的自身抗体,其中抗FcεRI抗体、抗IgE抗体在慢性特发性荨麻疹发病中的地位尤为重要。B淋巴细胞刺激因子可能参与慢性特发性荨麻疹自身抗体的形成。另外,部分慢性特发性荨麻疹患者HLA-Ⅱ类抗原的等位基因DRB1 04频率增加,提示该病发病具有自身免疫遗传基础。     

Evaluation of autologous plasma skin test in patients with chronic idiopathic urticaria

Background The pathophysiological mechanism of chronic urticaria is still poorly understood and its aetiology is considered to have an autoreactive basis. Autologous serum skin tests (ASSTs) and autologous plasma skin tests (APSTs) comprise the simplest ways for diagnosing autoreactive urticaria (with autoantibodies, histamine‐releasing factor and coagulation factors, especially thrombin) in a clinical setting. However, there are still some questions about the specificity of these tests. Objectives To evaluate the role of autoreactivity in the pathogenesis of chronic urticaria by means of measuring plasma prothrombin fragments 1 + 2, which are used as markers of thrombin, and to compare the APST with the ASST. Methods Forty‐two patients (19 men and 23 women; mean age 35·7 years, range 28–76) and 35 healthy volunteers (19 men and 16 women; mean age 30·3 years, range 20–80) were included in the study. APST, negative (ASST, sodium citrate, saline) and positive (histamine) control tests were performed in the patient and control groups. The levels of plasma prothrombin fragments 1 + 2 were also assessed. Results When the APST was evaluated without negative controls, it was positive in 67% of patients. However, the APST was positive in 0% when it was evaluated with negative controls. Levels of prothrombin fragments 1 + 2 were found to be elevated in patients with chronic idiopathic urticaria. Conclusions We suggest that as negative control tests were not performed along with the APST in previous studies, the APST showed a high rate of positivity. Thus, the use of APST for evaluating autoreactivity in clinical practice is not superior to the use of ASST and further studies should be conducted.     

慢性特发性荨麻疹患者外周血单一核细胞Toll样受体2和5 mRNA的表达

目的检测慢性特发性荨麻疹(CIU)患者外周血单一核细胞Toll样受体2和5 mRNA的表达.方法 收集45例CIU患者,38名正常人作为对照,采集PBMC提取RNA,应用逆转录聚合酶链扩增法检测Toll样受体2和5 mRNA表达水平.结果 CIU患者外周血单一核细胞Toll样受体2 mRNA表达水平低于健康对照组,分别为0.302±0.243和0.81±0.364(P＜0.01).Toll样受体5 mRNA表达水平低于对照组,差异有统计学意义,分别为0.558±0.342和0.722±0.350(P=0.035).结论 CIU患者外周血单一核细胞Toll样受体2和5 mRNA表达显著降低,提示CIU患者可能存在固有免疫异常.     

Helicobacter pylori and idiopathic chronic urticaria

BACKGROUND: Different studies have shown a high prevalence of Helicobacter pylori (HP) infection in patients with chronic urticaria (CU), and occasional remission of the skin lesions after eradication therapy. Recent investigations, however, have failed to find a significant relationship between the two conditions. We designed a case-control study to assess the prevalence of HP infection and the effect of bacterium eradication on the outcome of the skin disease in patients affected by CU. The literature is reviewed. METHODS: Twenty-five patients diagnosed with CU were included. Information about their medical history and a complete laboratory investigation ruled out other diseases or situations suspected to cause CU. Twenty-five healthy volunteers from a census-based, randomized sample were used as controls. HP infection was assessed by the (13)C-urea breath test (UBT). Eradication therapy included oral amoxicillin, omeprazole, and clarithromycin for 1 week. RESULTS: The high prevalence of HP infection (68%) and mean titer of UBT (24.13) in our patients with idiopathic CU do not differ from the general population. Marked differences were observed in the mean age of the CU patients with positive UBT (45.52years) vs. those without HP infection (35.25 years). After eradication therapy, only one patient showed a complete remission of urticaria and two showed a partial remission. CONCLUSIONS: Our results support a lack of relationship between HP infection and the course of idiopathic CU.     

Combined H1 and H2 antihistamine therapy in chronic urticaria

Chronic urticaria is a frustrating problem for the patient and the physician. The cause is usually undetermined, and the therapy is directed toward controlling symptoms. Recent evidence that human skin blood vessels possess H2 receptors, as well as the commonly recognized H1 receptors, suggests a possible reason for the frequent failure of H1 antihistamines in controlling this disorder. Eighteen patients with refractory chronic idiopathic urticaria participated in a double-blind, cross-over study to evaluate the efficacy of combined H1 (hydroxyzine hydrochloride) and H2 (cimetidine) antihistamines vs H1 antihistamines alone. This study indicates that combined H1 and H2 antihistamine therapy is statistically more effective than H1 antihistamines alone in controlling the symptoms of chronic urticaria.     

Clinical characteristics of pruritus in chronic idiopathic urticaria

BACKGROUND: Although pruritus is a predominant symptom of chronic idiopathic urticaria (CIU) its clinical characteristics have not been explored. OBJECTIVES: To characterize the clinical pattern and sensory and affective dimensions of the itch experience, utilizing a comprehensive itch questionnaire. METHODS: A structured questionnaire based on the McGill pain questionnaire was used in 100 patients suffering from CIU randomly recruited from a tertiary referral centre. RESULTS: All 100 patients recruited with CIU completed the questionnaire. In 68 patients pruritus appeared on a daily basis. Most patients experienced their pruritus at night and in the evening (n = 83), and 62 reported difficulty in falling asleep. Pruritus involved all body areas, but mostly the arms (n = 86), back (n = 78) and legs (n = 75). Accompanying symptoms were a sensation of heat in 45 patients and sweating in 15. Most patients (n = 98) were prescribed antihistamines (mainly sedating), of whom 34 experienced long-term relief. The sensation of itch was reported to be stinging (n = 27), tickling (n = 25) and burning (n = 23). Seventy-six patients found their pruritus bothersome, 66 annoying and 14 complained of depression. The itch intensity at its peak was more than double that felt after a mosquito bite. The worst itch scores of those who felt depressed were significantly higher than of those who did not (P = 0.018). There was a positive correlation between the sensory and affective scores during worst itch (P < 0.001). CONCLUSIONS: This study describes the itch experienced in CIU, highlighting sensory and affective dimensions. The itch questionnaire was found to be a valuable tool for evaluating pruritus in CIU and its unique features.     

Cathepsin G在慢性自发性荨麻疹患者血清中的表达

目的:研究组织蛋白酶G(cathepsin G)在慢性自发性荨麻疹患者血清中的表达变化,并初步探讨其作用。方法:纳入30例就诊前未经治疗的慢性自发性荨麻疹患者,设为观察组;另纳入30例健康体检者作为对照组。ELISA法检测两组血清中cathepsin G表达水平并进行比较。结果:对照组血清中cathepsin G浓度为(32.2±12.3)ng/m L,慢性自发性荨麻疹患者血清中cathepsin G浓度上调为(260.4±26.9)ng/m L,差异有统计学意义(t=42.26,P0.01)。结论:慢性自发性荨麻疹患者血清cathepsin G表达明显上调,其可能通过与多种细胞因子及炎症介质相互作用,参与慢性自发性荨麻疹的发病机制。     

Acquired cold urticaria: H1 and H2 antagonists versus cold induced histamine release

Three patients with idiopathic cold urticaria were treated with either or both cyproheptadine (Histamine H₁ receptor antagonist) and cimetidine (Histamine H₂ receptor antagonist). Cold induced histamine release (CIHR) was significantly higher in the patients (71.0 ± 23.8 pm/ml) than in normal volunteers (4.5 ± 1.0 pm/ml). Improvement of clinical manifestations with reduced CIHR was obtained by combination therapy using cyproheptadine and cimetidine but no favorable response was noted with either drug alone. The combined therapy with both drugs completely suppressed pruritis and edema but failed to suppress the erythematous reaction. Single cyproheptadine therapy was rather favored by the patients despite positive CIHR with the therapy. Histamine release from patients' leukocytes under three different conditions (37°C, 4°C→37°C, 4°C) was not significantly different.     

Not all chronic urticaria is "idiopathic"

Abstract: The aetiology of chronic urticaria in the majority of patients is elusive. The cause of physical urticarias (dermographism, delayed pressure urticaria, cold urticaria) is unkonown. We have identified a subset of chronic "idiopathic" urticaria patients, representing approximately 30% of the total in which the disease is caused by the presence of IgG autoantibodies against the high affinity IgE receptor (FcœRIα). This functional autoantibody stimulates normal (albeit vicarious) activation of mast cells and basophils via FcœRI, causing whealing and angioedema. Anti-FcœRI-positive patients are recognized by a combination of autologous serum skin testing and evoked histamine release from basophils of normal human donors. Autoantibody-positive and -negative patients are clinically indistinguishable and are treated routinely by combinations of H₁ and occasionally H₂-antihistamines in both cases. However, severely affected patients who are anti-FcœRI-positive can also be treated by non-specific immunotherapy (plasma pheresis, intravenous immunoglobulin, cyclosporin.