Treatment of patients with chronic idiopathic urticaria

Treatment of patients with chronic idiopathic urticaria (CIU) involves reducing symptoms with the least invasive therapy and carefully balancing risk and benefit. The mainstay of therapy is the use of antihistamines with or without the use of intermittent pulses of corticosteroids. Alternative therapies to chronic corticosteroids include leukotriene antagonists, plasma-phoresis, dapsone, stanazolol, hydroxychloroquine, methotrexate, cyclosporin, tacrolimus, and warfarin. A practical approach to CIU bases treatment and severity on the patients' previous response to therapy. Therapy goals are to reduce symptoms until spontaneous resolution occurs. Management of CIU patients can be both frustrating and rewarding.     

Mast cell heterogeneity in chronic idiopathic urticaria

Patients with chronic urticaria are more sensitive to codeine skin testing than other allergic individuals. Nonlesional skin in most patients with chronic urticaria was found to contain increased numbers of both total and atypical mast cells. The presence of increased mast cell density was found to correlate with the degree of clinical (dermatographism) and functional (codeine skin test) skin sensitivity.     

Immune profiles of patients with chronic idiopathic urticaria

Background: The immunologic characterization of chronic idiopathic urticaria (CIU) is still incomplete. In particular, it is not known if positivity to the intradermal autologous serum skin test (ASST) identifies an immunologic subset of CIU patients. Methods: Nineteen CIU patients and 15 healthy controls were enrolled in the study. A diagnostic flowchart was designed to select CIU patients, who were then analyzed by ASST. Cytokine and chemokine production and the expression of adhesion molecules was measured in patients and controls. Results: In CIU patients compared to controls, it was found that (1) TNF-alpha, IL-10, MIP-1alpha and RANTES production was augmented and IL-2 and INF-gamma reduced, and (2) CD44, CD11a and CD62L expression on CD4 and CD8 cells was augmented. Additionally, TNF-alpha and chemokine production was significantly increased in CIU patients with a negative ASST (p-; n = 10) compared to patients with a positive response to the test. Conclusions: The presence of an inflammatory process in CIU patients is suggested by the findings that the production of both TNF-alpha and chemokines as well as the expression of adhesion molecules is increased in these patients. Similarly to what is seen in rheumatoid arthritis, augmented IL-10 production might be secondary to the attempt to hamper the inflammatory milieu. Immune profiles are particularly altered in CIU p- patients, in whom a more aggressive therapeutic strategy might be considered.     

Food-additive-induced urticaria: a survey of 838 patients with recurrent chronic idiopathic urticaria

BACKGROUND: Recurrent chronic idiopathic urticaria (RCIU) is a common skin condition that affects 0.1-3% of the population in the USA and Europe and accounts for nearly 75% of all 'ordinary' chronic urticaria (CU) cases. METHODS: We studied 838 consecutive patients with RCIU referred to hospital between 1998 and 2003. Patients with known causes of CU were excluded. Clinical history, physical examination, and symptom diaries were evaluated during two periods, a diet-free period (1 week) and a food-additive-free diet (FAFD) period (4 weeks), respectively, and two double-blind placebo-controlled (DBPC) challenges of six food additives were administered. The first DBPC challenge included a mixture of the six food additives (DBPCmixed) given to all patients. The second DBPC challenge comprised the single food additives, administered at increasing doses (DBPCsingle) to patients with a positive DBPCmixed test and 105 patients with a negative DBPCmixed test, as a control. RESULTS: The DBPCmixed challenge was positive in 116 patients. None of the 105 control patients had a positive DBPCsingle test. Only 31 DBPCsingle tests were positive in patients with positive DBPCmixed challenge. Twenty-four of the 116 patients showing a positive DBPCmixed challenge also had a positive DBPCsingle result. CONCLUSIONS: Our results confirmed that food additive hypersensitivity reactions occurred in few RCIU patients using DBPCsingle challenge. The combination of the results of FAFD and DBPCmixed challenge seems to be of considerable practical interest for allergists, internists and dermatologists, rather than the data of clinical history and the results of DBPCsingle challenge, in patients with RCIU.     

Psychiatric morbidity and quality of life in patients with chronic idiopathic urticaria.

BACKGROUND: Chronic idiopathic urticaria (CIU) is a frequently occurring disease that has a great impact on the health-related quality of life (HRQL) of patients and seems to be associated with a number of psychological factors. OBJECTIVES: To determine the prevalence of psychiatric morbidity in patients with CIU and to determine HRQL of CIU patients compared with controls. METHODS: A semistructured interview form, a generic form of the HRQL questionnaire (Medical Outcomes Study 36-Item Short-Form Health Survey [SF-36]), and the Structured Clinical Interview for DSM-IV Axis Disorders (SCID-I) were administered to CIU patients who presented to the Allergy Department of the University of Istanbul (from January 1 to April 30, 2005). Healthy subjects matched sociodemographically with the study group were used as the control group. RESULTS: Eighty-four CIU patients and 75 controls were included in the study. The mean +/- SD age of the study participants was 36.83 +/- 10.26 years, and 84% were women. The mean +/- SD duration of the disease was 6.34 +/- 7.2 years, and symptoms were intermittent in 51%. The SCID-I revealed a psychiatric diagnosis in 60% of the patients. In terms of the distribution of psychiatric diagnoses, the most frequently occurring diagnosis was depressive disorders (40%). Most patients (81%) believed that their illnesses were due to stress. The subdomains on the SF-36 measurements were significantly lower than those of the control subjects (P < or = .005). The physical function, vitality, and mental health subdomains of the SF-36 in the patients with a psychiatric diagnosis were significantly lower (P < .05). CONCLUSION: These findings suggested that psychiatric morbidity is high among ICU patients and is detrimental to their quality of life.     

Efficacy and safety of sulfasalazine in patients with chronic idiopathic urticaria

BackgroundThere are limited data regarding alternative treatments for antihistamine refractory chronic idiopathic urticaria (CIU). Patients with recalcitrant skin disease often cannot gain satisfactory symptom control with standard therapies and may require prolonged courses of oral corticosteroids. There is a lack of information describing the degree and duration of sulfasalazine's efficacy, the frequency and nature of adverse reactions, and the appropriate safety monitoring parameters.ObjectiveTo present a case series detailing the efficacy and safety of sulfasalazine therapy in patients with CIU.MethodsA retrospective chart review was conducted of 39 patients with sulfasalazine-treated CIU evaluated at Johns Hopkins Asthma and Allergy Center from October 2007 to March 2012. Eight patients were excluded from the final analysis.ResultsTwenty-six patients (83.9%) showed an improvement in symptoms within the first 3 months, with 51.6% of patients (n = 16) becoming asymptomatic within the first 6 months of starting sulfasalazine. Eleven patients (35.4%) achieved complete relief of symptoms after tapering off sulfasalazine therapy. Five of the 31 patients (16.1%) failed treatment, defined as worsening symptoms and pursuit of an alternative therapy. Six of 31 patients (19.4%) had a modified course of sulfasalazine therapy owing to abnormal hematologic parameters. Serious adverse events leading to drug discontinuation occurred in 6.5% of patients (n = 2) and included a patient with drug-induced leukopenia and one with rhabdomyolysis.ConclusionSulfasalazine is a highly effective treatment for patients with antihistamine resistant CIU. The frequency of adverse events leading to an alteration of sulfasalazine treatment supports the need for close monitoring of these patients.     

Effects of systemic corticosteroids on cutaneous histamine secretion and histamine-releasing factor in patients with chronic idiopathic urticaria

Background Enhanced skin mast cell releasability of histamine, increased production of histamine releasing factor (HRF), and cutaneous inflammatory process are the hallmarks of chronic idiopathic urticaria (CU). Although H₁-antihistamines are known to alleviate the symptoms effectively in most cases, systemic corticosteroids (CS) are given in more resistant patients. Their mode of action remains a matter of controversy. Objectives In the present study, the effects of a 7-day course of CS or placebo on histamine content and HRF production iti non-lesional skin of 19 CU patients were examined. Methods Using the skin chamber technique, HRF production and histamine content were assessed in normal-appearing skin of patients with CU over a 2-h observation period. Those two parameters were measured before and after treatment, in a double-blind fashion. Results No significant changes occurred in any parameters after placebo treatment. In contrast with this, significant decrease of HRF activity was observed after 1 week of oral methylprednisolone while no change was documented for histamine secretion. Conclusion These data suggest that CS therapy improves symptoms of CU in association with a decreased production of HRF in uninvolved skin.     

Treatment of chronic idiopathic urticaria with terfenadine

The usefulness of antihistamines is impaired by their sedative side effects. In a double blind crossover study of twenty-four patients with chronic idiopathic urticaria, we have found terfenadine to be a non-sedative and highly effective drug.     

Elevated serum B-cell activating factor in patients with chronic urticaria

The B and T cells abnormalities that have been described among CU patients, lend support to its regard as an autoimmune disease. In this study we compared serum B-cell activation factor (BAFF) levels in 46 CU patients to 24 healthy controls and evaluated a possible association between elevated serum BAFF in CU patients and the presence of autologous serum skin test, anti-thyroid antibodies, antinuclear antibodies, high total IGE levels, and urticaria disease severity. We found that serum BAFF levels is elevated statistically significant in CU patients compared to healthy control (1228±342 pg/ml vs. 758±313 pg/ml, P<0.0001). CU patients with severe disease activity had significantly higher serum BAFF levels compared to patients with mild CU (1394.6±299.6 vs. 1097.6±221.3, P=0.0008). No association was found between the presence of positive autologous serum skin test, anti-thyroid antibodies or antinuclear antibodies or high levels of total IgE and serum BAFF levels in CU Patients. We conclude that CU patients have higher levels of serum BAFF which associate with disease severity.     

Successful treatment of autoimmune chronic idiopathic urticaria with intravenous cyclophosphamide.

BACKGROUND: A 45-year-old woman presented with a 20-year history of chronic idiopathic urticaria (CIU) unresponsive to H1- and H2-antagonists and combinations of other anti-inflammatory agents but controlled with daily prednisone (35 mg) for more than 13 years. Intracutaneous testing to autologous serum revealed an 8 x 10-mm wheal/flare reaction consistent with the presence of anti-Fc epsilonRIalpha autoantibodies. These autoantibodies have been reported to be present in >45% of patients with CIU. Their functional role in the pathogenesis of CIU remains poorly understood. OBJECTIVE: Because of the therapeutic refractory nature of this patient's CIU requiring high doses of corticosteroids, it was decided to initiate treatment with intravenous cyclophosphamide (CTX) in an attempt to eradicate autoantibody-producing B-lymphocyte clones. This therapeutic approach has been previously successful in other autoantibody-mediated disorders such as type II acquired angioedema and factor VIII deficiency. RESULTS: Initial treatment consisted of 500 mg CTX intravenously followed by increases of 100 mg every 2 weeks, with the maximum dose reaching 1,500 mg once a month, which represents approximately 20% of the dose administered during systemic cancer chemotherapy. Within 7 months there was a complete clinical remission and prednisone was discontinued. Repeat intracutaneous testing to autologous serum was negative, consistent with an abrogated autoantibody response. The patient has not experienced a recurrence of CIU at the time of this report. CONCLUSION: This index case suggests that intravenous CTX may be effective in alleviating autoantibody-associated CIU in corticosteroid-dependent patients refractory to conventional therapies.     

Cyclosporin A in patients affected by chronic idiopathic urticaria: a therapeutic alternative.

Chronic Idiopathic Urticaria (CIU) is a cutaneous disorder for which there is no identifiable specific etiologic agent. Some recent evidences suggest that CIU might be an autoimmune disease. We analyzed immunological features occurring in CIU and evaluated effectiveness and tolerance of Cyclosporin A (CsA) treatment in patients unresponsive to antihistaminic treatment. Twenty patients with CIU were recruited after a selective diagnostic protocol and were divided into two groups. CsA was prescribed for group 1 and Prednisone for group 2 as control, for 8 weeks. Before and after the therapy we performed on all patients immunological studies. For all patients symptoms disappeared after a few days of therapy. Before therapy all patients showed activated B cells (CD19+CD23+ cells) and among B CD19+ cells, about 20% were CD5+ (cells that synthesize natural autoantibodies). After treatment with Prednisone in group 2, a significant reduction of CD4+ lymphocytes (p = 0,01) was observed. Our findings might support the CIU autoimmune pathogenetic hypothesis. The clinical remission in the CsA-treated group confirmed the therapeutic effectiveness of this therapy in antihistaminic unresponsive CIU and, at dosage used, side effects were rare, mild and reversible. Thus, CsA might be a good therapeutic alternative in CIU patients unresponsive to conventional treatments.     

Histologic studies of chronic idiopathic urticaria

Skin biopsy specimens were obtained from 43 consecutive patients with chronic idiopathic urticaria and from seven normal controls. Of 43 patients, 42 had a non-necrotizing perivascular infiltrate composed primarily of mononuclear cells. There was no evidence of damage to vessel walls, of nuclear debris, or of extravasation of red blood cells, and most cells were seen around vessels rather than within the vessel wall. One patient had vasculitis with a neutrophilic infiltrate, nuclear debris, and positive immunofluorescence. Quantitative cell counts revealed four times the number of mononuclear cells and 10 times the number of mast cells in urticaria biopsy sites vs normal skin. Thus chronic urticaria is characterized by an accumulation of mononuclear cells and mast cells with mast cell degranulation presumably associated with hive formation. In our series, the characteristic lesion is not vasculitic. The stimulus responsible for the infiltration of skin with these cells is unknown.     

Circulating level of the platelet-derived CXC chemokine platelet factor 4 in chronic urticaria patients with or without coexistent euthyroid Hashimoto's thyroiditis

The concept of autoimmune aetiology of some cases of chronic urticaria (CU) has been supported by several observation including wheal-and-flare reaction induced by intradermal injection of autologous serum as well as association with other autoimmune diseases, in particular Hashimoto's thyroiditis (HT). It is known that activated platelets may actively participate in immune-inflammatory processes. Therefore, we assessed whether autoimmune phenomenon associated with CU influence the systemic platelet activity measured by circulating level of platelet factor 4 (PF-4). Plasma level of PF-4 was analysed using enzyme-linked immunosorbent assay in twelve women with strong positive response to autologous serum skin test (ASST) suffering from CU, twelve female patients with strong positive ASST suffering from both CU and untreated, HT as well as sixteen healthy women. All the subjects were clinically and biochemically euthyroid. There were no statistically significant differences between the CU patients with or without euthyroid HT and plasma PF-4 level in healthy controls. In patients with both CU and thyroiditis, plasma level of PF-4 did not correlate significantly with the level of antibodies against thyroperoxidase. It seems that circulating level of the platelet-derived chemokine is not increased in CU patients with positive response to ASST, regardless the occurrence of euthyroid HT.     

Desloratadine in the treatment of chronic idiopathic urticaria

Chronic idiopathic urticaria (CIU) is a common dermatologic disorder that may severely impair quality of life. Patients may suffer symptoms such as pruritus and disfigurement due to wheals for years or decades. Advances have been made in the last 10 years with the identification of an autoimmune pathogenesis in a significant proportion of patients. Despite this, treatment remains symptomatic, and antihistamines are the first choice of therapy once the diagnosis of CIU has been established. The goal of treatment is rapid, long-lasting symptom relief, and currently available antihistamines fail to provide this in many cases. Desloratadine is a novel, potent H₁-receptor antagonist with additional inhibitory effects on inflammatory mediators such as cytokines and adhesion molecules. Newly published data on the efficacy and safety of desloratadine in CIU is highly encouraging, suggesting that the drug may improve symptom control above that currently available.     

Prolonged benefit in the treatment of chronic idiopathic urticaria with astemizole

A double-blind clinical trial of 51 patients with chronic idiopathic urticaria using oral astemizole for 8 weeks demonstrated significant improvement in symptoms and lesions in 75% of treated patients versus 20% in the placebo group. The suppression of urticaria persisted for an average of 38 days, demonstrating the long duration of action of astemizole.