Resolution of chronic urticaria in patients with thyroid autoimmunity

Background: Autoimmune disease has been implicated as a cause of chronic urticaria, and anti-thyroid antibodies have been found in patients with chronic urticaria. Because some patients with chronic urticaria and autoimmune hypothyroidism have had clinical resolution with thyroid hormone replacement, we investigated the effect of thyroid hormone in euthyroid patients with chronic urticaria and thyroid autoimmunity. Methods: Ten euthyroid patients with refractory hives were treated with thyroxine. Seven patients had elevated anti-thyroid antibodies at baseline. Thyroid function and anti-microsomal and anti-thyroglobulin antibody levels were monitored during treatment. If a clinical response was achieved, thyroxine was discontinued and restarted if symptoms recurred. Results: Seven patients with elevated anti-thyroid antibodies reported resolution of symptoms within 4 weeks. Three patients without elevated anti-thyroid antibodies did not respond. Five patients had a recurrence of symptoms after treatment was stopped, which resolved after treatment was restarted. Thyroid-stimulating hormone levels decreased in all patients with a clinical response. No correlation between clinical resolution and anti-thyroid antibody levels was seen. Conclusion: Thyroid autoimmunity in euthyroid patients may be associated with chronic urticaria, and treatment with thyroid suppression can result in clinical remission. (J ALLERGY CLIN IMMUNOL 1995;96:901-5.)     

Successful treatment of chronic idiopathic urticaria and angioedema with cimetidine alone

We have studied a 50-year-old white man with chronic urticaria and angioedema who has responded to treatment with cimetidine alone for over 2 yr. In a double-blind, placebo-controlled study, cimetidine alone was at least as effective as chlorpheniramine in relief of urticaria and angioedema. Additionally, cimetidine significantly inhibited (p less than 0.01) the wheal response to histamine when it was compared to placebo. The inhibition of wheal response to histamine by cimetidine was significantly higher (p less than 0.05) than chlorpheniramine. The presence of predominantly H2- rather than H1-histamine receptors in the cutaneous blood vessels may be responsible for the therapeutic effects of cimetidine in this patient.     

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.     

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.     

Hereditary angioedema and thyroid autoimmunity.

Sera from 91 patients with hereditary angioedema were screened for thyroid antibodies. The results for the 77 patients more than 17 years old were compared with previously published data for the prevalence of thyroid disease in a large community (Whickham). Of the female patients with hereditary angioedema, the prevalence of thyroglobulin antibodies (TGA) was 14.0%, higher than the expected 3% (p less than 0.001). The prevalence of thyroid microsomal antibodies (TMA) was 20%, also higher than the expected 7.6% (p less than 0.01). The age distributions of the females in both groups differed: in the group with hereditary angioedema there was a greater proportion of younger patients which should have resulted in a lower prevalence of thyroid antibodies. Adjusting for related patients with hereditary angioedema, there was still an increased prevalence of TGA (p less than 0.01) and TMA (p less than 0.01).     

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.     

Hyperthyroidism and polycythemia vera with chronic urticaria and angioedema

Of 154 patients with chronic urticaria, six manifested concomitant hyperthyroidism and four polycythemia vera. Investigations of serum IgE, immune complex quantitation, complement and skin biopsies failed to elucidate a causal relationship. Polycythemia vera and hyperthyroidism should be considered as possible associations in the evaluation of chronic urticaria.     

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.     

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.     

Circulating stem cell factor in patients with chronic idiopathic urticaria.

BACKGROUND: The nature of histamine-releasing factors involved in the pathogenesis of chronic idiopathic urticaria (CIU) is still controversial, since functional IgG autoantibodies specific for the high-affinity IgE receptor, Fc(epsilon)RI, can be detected in only 20% of patients showing a strong skin reactivity on the autologous serum skin test. The absence of systemic eosinophilia in CIU patients, along with the increase in mast cells in skin biopsy specimens, suggests a possible role for stem cell factor (SCF), the only cytokine/growth factor known to induce mediator release from human mast cells. OBJECTIVE: To investigate the possible role of SCF as a histamine-releasing factor in patients with CIU. METHODS: The SCF levels were measured in serum samples from 65 patients with CIU who scored strongly positive on the autologous serum skin test; of these patients, 32 had negative results and 33 had positive results on in vitro histamine release assay by a quantitative commercial sandwich immunoassay technique. Serum samples from 40 healthy subjects were used as controls. RESULTS: Serum SCF levels in all 65 CIU patients did not differ from those found in healthy controls. No difference in SCF levels was found between patients with positive and negative results on histamine release assay. CONCLUSIONS: An increase in serum SCF levels does not play a pathogenic role in CIU.     

Chronic idiopathic urticaria: a family study.

BACKGROUND: Genetic factors play a pivotal role in the pathogenesis of many autoimmune disorders. Recent studies demonstrated that chronic idiopathic urticaria (CIU) is an autoimmune disease at least in a subset of patients, but familial studies have not yet been conducted. OBJECTIVE: To investigate the familial pattern of CIU. METHODS: One thousand three hundred eight adults with CIU (aged >12 years; male/female 388/920) seen during the last 10 years were thoroughly interviewed to ascertain the presence of CIU among first-degree relatives. Positive histories were confirmed by medical recordings. Proportions were compared with those expected in the general population on the basis of a 0.1% prevalence of the disease. RESULTS: Fifty-six of 1,308 (4%) patients had a familial history of CIU affecting at least one first-degree relative. This number exceeded by approximately eight times the expected one (P < 0.001). Twenty-two of 23 (96%) patients with a positive familial history were positive on autologous serum skin test (P < 0.01 by comparison with previous studies). CONCLUSION: The observation that CIU is much more frequent among first-degree relatives of affected individuals than in the general population suggests the existence of a genetic background for the disease and provides a clinical support to the reported association between CIU and human leukocyte antigen DR4. Ninety-six percent of patients with a positive familial history were positive on autologous serum skin test, a condition that has been associated with the presence of circulating histamine releasing factors, including anti-Fc epsilonRI or anti-immunoglobulin E antibodies.     

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.     

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.     

BSACI guideline for the management of chronic urticaria and angioedema

This guidance for the management of patients with chronic urticaria and angioedema has been prepared by the Standards of Care Committee of the British Society for Allergy and Clinical Immunology (BSACI). The guideline is based on evidence as well as on expert opinion and is aimed at both adult physicians and paediatricians practising in allergy. The recommendations are evidence graded. During the development of these guidelines, all BSACI members were included in the consultation process using a Web‐based system. Their comments and suggestions were carefully considered by the Standards of Care Committee. Where evidence was lacking, a consensus was reached by the experts on the committee. Included in this management guideline are clinical classification, aetiology, diagnosis, investigations, treatment guidance with special sections on children with urticaria and the use of antihistamines in women who are pregnant or breastfeeding. Finally, we have made recommendations for potential areas of future research.