Serum IgA contributes to the comprehension of Anisakis simplex associated chronic urticaria.

The phenotype of allergic diseases associated with Anisakis determines the pattern of cytokines related to antibody production. However, the role of serum IgA and the immunomodulatory mechanisms exerted by active infection of L3 or passive mucosal contact with A. simplex specific antigens has not been studied before. We measured serum cytokine by flow cytometry (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, IL-17A, TGF-ß1) and antibody levels (IgE, IgG4, IgA) by ELISA against total and excretory-secretory (ES) antigens, Ani s 3,and the group of major allergens Ani s 1, Ani s 7, and Ani s 13 in sera from 10 patients with gastro-allergic anisakiasis (GAA), 11 Anisakis sensitization associated chronic urticaria (CU+) as well as 17 non-Anisakis-sensitized patients with chronic urticaria (CU-), compared with the urticaria control group (18 subjects). Specific IgE, IgG4 and IgA were high in the GAA, but IgA levels were significantly higher in the CU+ with respect the CONTROL group. We observed higher levels of the ratio IgA/IgG4 in CU+ than GAA group for Ani s 1, Ani s 7, Ani s 13 and ES. Furthermore, chronic urticaria (CU) patients showed significant lower levels of IL-10, IFN-γ and IL-17A than patients without CU. The anti-Ani s 13 IgA/IgG4 ratio correlated positively with pro-inflammatory cytokines and ratios (TNF-α, IL-17A, Th17/Th2, Type1/Type2 and TNF-α/IL-10) in CONTROL group. In general, Anti-Anisakis IgA/G4 ratio was high in CU patients. In conclusion, this study demonstrates the importance of serum IgA because it is associated with chronic urticaria independently of Anisakis sensitization.

Effects of the immunoglobulin/histamine complex on panic disorder concurrent with chronic spontaneous urticaria: a case report.

BACKGROUND: Panic disorder and panic attacks are two of the most common problems in psychiatry. A psychoimmunological correlation between allergic diseases and panic disorder has been strongly suggested. Histamine H1 receptor antagonists have been suggested as alternative drugs for the treatment of panic disorder. Chronic spontaneous urticaria (CSU) and panic disorder improved simultaneously with selective serotonin reuptake inhibitor antidepressants. Panic disorder has also been treated with the antihistamine chlorpheniramine. The immunoglobulin/histamine complex is a histamine-fixed immunoglobulin preparation that was reported to be effective in treating CSU. This case report describes the successful treatment of a patient with concomitant panic disorder and CSU for 23 years using immunoglobulin/histamine complex therapy. CASE PRESENTATION: This report describes a 52-year-old female Korean patient who suffered from CSU with panic disorder for 23 years. Basic allergy tests (blood tests and skin prick tests) were conducted before and after treatment for the evaluation of allergic conditions. A multiple allergosorbent test (MAST) for the detection of allergen-specific IgE levels was also performed. The clinical severity of CSU was evaluated using the urticaria severity score system. Diagnostic interviews systematically assessed the diagnostic criteria outlined by the DSM-V, and the patient was evaluated before, during and after treatment using the Beck Depression Inventory (BDI-2) for depression, the State-Trait Anxiety Inventory (STAI) for anxiety and the Beck Hopelessness Score (BHS) for hopelessness. The patient received 2 ml of Histobulin™ (12 mg human immunoglobulin/0.15 µg histamine complex) once a week by subcutaneous injection for the treatment of CSU. Initial improvement of CSU was achieved after the third injection. After the twenty-seventh injection of Histobulin™, she showed no symptoms or signs and ceased allergic medication use. With the remission of CSU, allergic rhinitis was also completely resolved. The frequency of the common cold was significantly decreased during and after treatment. The medication frequency and development of clinical manifestations of panic disorder changed in parallel with the clinical severity of CSU. Moreover, the patient exhibited no clinical manifestations and ceased medication for panic disorder and sleeping pills for insomnia simultaneously with the remission of CSU. In the psychological evaluation, the BDI, STAI and BHS scores improved accordingly. CONCLUSIONS: The immunoglobulin/histamine complex was effective in treating CSU and concomitant panic disorder in this patient and could be effective in treating some types of panic disorder. Considering the mechanisms of action of histamine and the immunoglobulin/histamine complex together with the patient's clinical progress, histamine seemed to be related to panic disorder in this case. The concept of histamine-mediated syndromes, including allergies and psychiatric disorders, shows that a wider disease identity may be needed. Further studies on the immunopathogenesis of panic disorder and the mechanisms of action of the immunoglobulin/histamine complex are necessary.

Chronic Urticaria in Older Adults: Treatment Considerations.

Chronic urticaria is characterized by recurrent wheals and/or angioedema lasting for more than 6 weeks. Chronic urticaria is an extremely disabling disease limiting daily activities, compromising patient quality of life, and frequently associated with psychiatric comorbidities (depression and/or anxiety). Unfortunately, there are still gaps in the knowledge regarding treatment in special populations, especially in older patients. Indeed, there are no specific recommendations for the management and treatment of chronic urticaria in older people; therefore, recommendations for the general population are used. However, the utilization of some medications may be complicated by potential concerns of comorbidities or polypharmacy. Currently, the diagnostic and therapeutic procedures for chronic urticaria in the older patient are the same as those indicated for other age groups. In particular, there is a limited number of blood chemistry investigations for spontaneous chronic urticaria and specific tests for inducible urticaria. With regard to therapy, second-generation anti-H1 antihistamines are used and, in recalcitrant cases, omalizumab (an anti-IgE monoclonal antibody) and possibly cyclosporine A are additional choices. Nonetheless, it should be underlined that in older patients the differential diagnosis can be more difficult, owing to the lower frequency of chronic urticaria and the likelihood of other pathologies that are peculiar for this age group and that can be included in the chronic urticaria differential diagnosis. As far as therapy is concerned, the physiological characteristics of these patients, the possible comorbidities, and the intake of other medications often require a very attentive drug selection for chronic urticaria compared with other age groups. The purpose of this narrative review is to provide an update on the epidemiology, clinical characteristics, and management of chronic urticaria in older patients.

Clinical features of patients with chronic spontaneous urticaria associated with autoimmune thyroiditis.

The aim of the study was to focus on children with both chronic spontaneous urticaria (CSU) and autoimmune thyroiditis (AT) as this topic is rarely studied in children although some publications show a higher proportion of antithyroid antibodies in children with CSU. We highlight two cases of children with both CSU and AT and compare their data with reports from the literature. Since only case reports or case series were available, we performed a descriptive analysis of 15 patients. There were 7 (46.7%) cases of hypothyroidism and the rest were euthyroid. Hypothyroidism appears before, during, and after the diagnostic of CSU. One patient with hypothyroidism and one with euthyroidism receiving l-thyroxine experienced remission of urticaria. Three patients over 12 years of age (20%) received omalizumab. Three patients (20%) had another autoimmune disease and seven (58.3%) had a family history of thyroid disease or autoimmune disease. CONCLUSION: Children with CSU need repeated testing for antithyroid antibodies. Children with both CSU and AT require close medical supervision focused on the development of other autoimmune diseases. l-thyroxine may improve urticaria in patients with hypothyroidism, but there is not enough evidence for patients with euthyroidism. Omalizumab may be of benefit in this population but well-controlled studies in children with AT and CSU are needed.

Chronic Spontaneous Urticaria in Patients With Interstitial Cystitis/Bladder Pain Syndrome: Insights From Big Data Analyses.

OBJECTIVE: To examine the association between chronic spontaneous urticaria (CSU) and interstitial cystitis/bladder pain syndrome (IC/BPS). METHODS: A population-based retrospective cross-sectional study was performed using the Clalit Health Services medical database. The prevalence of CSU was compared between patients diagnosed with IC/BPS and age- and gender-matched controls. Univariate analysis was performed using Chi-square and Student t test and a multivariable analysis was performed using a logistic regression model. RESULTS: The study included 681 patients with IC/BPS and 3376 demographically matched controls. The mean age of IC/BPS patients was 60 years old. The prevalence of CSU among patients with IC/BPS was higher as compared to the control group (20% vs 13.7%; P <.001). The adjusted OR for CSU in patients with IC/BPS was 1.58 (95% CI 1.28-1.97). Female gender and Jewish ethnicity were associated with the coexistence of these disorders (OR 1.7 95% CI 1.36-2.13, and 1.6 95% CI 1.28-2, respectively). CONCLUSION: A significant association was found between IC/BPS and CSU. This finding may support the presence of allergic/immune components in the pathogenesis of IC/BPS.

A case report of hypocomplementemic urticarial vasculitis presenting with membranoproliferative glomerulonephritis.

BACKGROUND: Hypocomplementemic urticarial vasculitis syndrome is an infrequent condition characterized by ocular, renal, gastrointestinal and pulmonary involvement with low serum complement levels and autoantibodies. Renal manifestations vary from microscopic hematuria to nephrotic syndrome and acute kidney injury. Accordingly differing histologic patterns have been reported. CASE PRESENTATION: We present the case of a 65 years old woman with a history of chronic uveitis who presented with arthralgias, urticarial rush, nephrotic syndrome, glomerular hematuria and low serum complement. Kidney biopsy revealed an immune-complex membranoproliferative glomerulonephritis. The patient received induction therapy with steroids, cyclophosphamide and hydroxychloroquine followed by rapid clinical improvement and remission of proteinuria. Maintenance treatment consisted of rituximab pulses. CONCLUSIONS: The majority of hypocomplementemic urticarial vasculitis syndrome cases is idiopathic, although an association to drugs, infections or other autoimmune disorders has been recorded. Given the rarity and heterogeneity of the disease, no standard treatment is established.

Investigation of Autoimmune Disease in Children with Chronic Spontaneous Urticaria.

INTRODUCTION: Chronic spontaneous urticaria (CSU) in childhood affects the quality of life of the patient and may be associated with other autoimmune diseases. The aim of this study was to investigate the association of autoimmune diseases with CSU in children. METHODS: In a 3-year period, from 2015 to 2018, forty-nine children were diagnosed with CSU and monitored in the Outpatient Pediatric Allergy Clinic of the University Hospital of Ioannina in Northwestern Greece. The comorbidity with other autoimmune diseases was investigated in this population by autoantibody evaluation. RESULTS: Of the 49 children with CSU, 1 had autoantibodies for celiac disease (CD), which was confirmed by duodenal biopsy via gastroscopy. Four children had high serum levels of anti-thyroid peroxidase antibodies but normal thyroid function. No other specific autoantibodies were detected. CONCLUSION: The prevalence of autoimmune diseases among our children with CSU was low. Nevertheless, we think it is important to test children with CSU for other autoimmune diseases. CD can be diagnosed in children with CSU even in the absence of other indicative signs.

[Chronic superficial urticaria associated with solid cancers: Case report and literature review]. / Urticaire chronique superficielle associée aux cancers solides : un cas et revue de la littérature.

BACKGROUND: Chronic urticaria is common and is generally idiopathic ("spontaneous"). Links between solid cancer and chronic urticaria have been mentioned in the literature. PATIENTS AND METHODS: We report the case of a 63-year-old man presenting with superficial chronic urticaria associated with adenocarcinoma of the ethmoid sinus. We discuss the possibility of systemic origin in light of the severity of the disease and its resistance to treatment. Only recurrent ethmoidal cancer was highlighted. Curative care resulted in complete resolution of the urticaria without relapse at 32 months of follow-up. DISCUSSION: In a literature review, we collected 17 cases of superficial chronic urticaria associated with cancer. These cases were marked by synchronous progression and by the inefficacy (86%) of anti-histamines and systemic corticosteroids. Although cases of chronic superficial urticaria associated with cancer remain rare, the condition merits discussion due to its severity and significant resistance to therapy.

Chronic urticaria and osteoporosis: a longitudinal, community-based cohort study of 11 944 patients.

BACKGROUND: Chronic urticaria (CU) carries many risk factors for osteoporosis, but data on the relationships between CU and osteoporosis are lacking. OBJECTIVES: To evaluate the association between CU and osteoporosis in a large community-based study. METHODS: A nationwide observational longitudinal cohort study was conducted. CU was defined as four pairs of urticaria diagnoses; each pair was recorded within a period of 6 weeks and was registered by physicians in a primary-care setting. Patients with CU and their age- and sex- matched controls were followed for the incidence of osteoporosis and other laboratory data between 2002 and 2017. Data regarding systemic steroid exposure and other relevant risk factors for osteoporosis were obtained. Analyses of risk for osteoporosis were performed in Cox regression models adjusted for age, sex, exposure to systemic corticosteroids, obesity, smoking and hyper- and hypothyroid disease. RESULTS: The study included 11 944 patients with CU and 59 829 controls. During the study's observation period, 1035 (8·7%) patients with CU were diagnosed with osteoporosis, compared with 4046 (6·8%) controls. The adjusted multivariate analysis demonstrated that CU was significantly associated with a higher risk for osteoporosis (hazard ratio 1·23, 95% confidence interval 1·10-1·37, P < 0·001). CONCLUSIONS: CU may impose a risk for osteoporosis. Appropriate targeted screening should be considered.