Sami Ozturk

Heart Rate Variability in Patients with Allergic Rhinitis

Considering the role of autonomic imbalance in the pathogenesis of hypersensitivity reactions, we evaluated the autonomic system through time-domain analysis of heart rate variability (HRV) in patients with allergic rhinitis. Twenty-four patients with allergic rhinitis and 22 healthy subjects (mean age, 41 +/- 8 years and 37 +/- 9 years, respectively) were enrolled in the study. The diagnosis of allergic rhinitis was based on the history, symptoms, and skin prick tests results. Twenty-four-hour ambulatory electrocardiographic recordings were obtained, and the time-domain indices were analyzed. Analysis of HRV revealed that the SD of normal RR intervals, SD of successive differences in normal cycles, and HRV triangular index were not significantly different between the groups, but the root mean square successive difference, number of RR intervals exceeding 50 milliseconds, and percentage difference between adjacent normal RR intervals exceeding >50 milliseconds were significantly greater in the study group, compared with the control group. Our findings showed that HRV indices, which predict parasympathetic predominance, were increased in patients with allergic rhinitis. This finding shows that vagal activation is present not only in the nose but also in other systems, including the cardiovascular system.

The role of ace gene polymorphism in the development of angioedema secondary to angiotensin converting enzyme inhibitors and angiotensin II receptor blockers

BACKGROUND Angiotensin Converting Enzyme inhibitors (ACEi) may cause angioedema, with an incidence of 0.1 % to 1 %, which may be life-threatening. ACEi induce angioedema by increasing the levels of bradykinin. Angiotensin II receptor blockers (ATRB), have a pharmacological profile similar to ACEi. The polymorphism of the ACE gene is based on the presence or absence of a 287-bp element on intron 16 on chromosome 17. The plasma level of ACE is related to gene polymorphism. ACE level in genotype DD is double that in genotype II. OBJECTIVE The aim of this study was to investigate whether the relationship between ACE gene polymorphism and ACEi induced angioedema is present or not. METHODS ACE gene polymorphism was investigated in patients with angioedema due to the use of ACEi or ATRB (n:32, group 1), in patients receiving ACEi or ATRB without angioedema (n:46, group 2), and healthy controls (n:96, group 3). RESULTS ID polymorphism was the most frequent genotype in all groups, without any significant difference among the groups (p:0.868). ACE gene polymorphism was not related with the drugs used (ACEi or ATRB), localisation of angioedema, and female sex, in group 1. CONCLUSION Our results showed that ACE gene polymorphism has no effect on ACEi or ATRB induced angioedema.

Serum Leptin Levels and Lipid Profiles in Patients with Allergic Rhinitis and Mild Asthma

BACKGROUND Despite improved understanding of the pathophysiology of allergic rhinitis and asthma, the effect of serum leptin level is still controversial. Only a few studies have been performed to investigate the serum leptin levels in allergic rhinitis and asthma, and contradictory results have been observed. OBJECTIVE We aimed to investigate the association between leptin, lipid profiles and allergic rhinitis and mild asthma, and to determine whether inhaled and/or intranasal steroids affect the leptin levels. PATIENTS AND METHODS We studied 43 patients with allergic rhinitis (10 of with mild asthma) (mean age 29.81, range 18-45 yr) and 32 volunteers as a control group (mean age 30.53, range 20-45 yr). RESULTS Serum leptin levels in patients were 8.49 +/- 10.76 microg/ml, and did not differ from volunteers 5.42 +/- 6.63 microg/ml. (p > 0.05). We found a direct link between increased body mass index (BMI) and serum leptin levels (p = 0.008). No association was seen between leptin and triglyceride, HDL-cholesterol, VLDL-cholesterol, eosinophil, total IgE (p > 0.05); except for total cholesterol and LDL-cholesterol (p < 0.05). Although, no correlation between allergic rhinitis and mild asthma and serum level of leptin was shown, these parameters and age correlations were stronger in female than in male (p = 0.39 for male and p = 0.011 for female), and also found direct link between increased BMI and sex and patients group (p = 0.008 for male and p = 0.0001 for female). We also determined that there was no effect of inhaled and/or intranasal steroids statistically on serum leptin levels. CONCLUSION Our data demonstrate that the serum levels of leptin and lipid profiles on allergic rhinitis and mild asthma were not different than those in controls.

Healing effects of omalizumab in a patient with cholinergic urticaria associated severe dyspeptic complaints.

To the Editor: Cholinergic urticaria (CU) is a type of physical urticaria characterized by a number of short-lasting, highly pruritic weals. The underlying pathological mechanism of CU is not fully understood.[1] Omalizumab is a humanized, monoclonal IgG anti-IgE antibody that binds specifically to circulating IgE molecules, thus interrupting the allergic cascade.[2] The efficacy of anti-IgE treatment has been shown in many disorders with complex and unclear etiology, comprising physical urticarias, chronic idiopathic urticaria, angioedema and eosinophil-associated gastrointestinal disorders.[3] A 38-year-old Caucasian male with severe CU was presented to GATA Haydarpasa Training Hospital in September 2014. Severe dyspeptic complaints including epigastric pain and upper abdominal fullness were accompanied the urticarial lesions for 6 months. He mentioned that approximately 20–30 min after many kind of foods and mild exercise severe pruritic hives took place, especially on the trunk and upper extremities [Figure 1]. He also indicated that the dyspeptic complaints were not improved by use of H2 receptor antagonists or proton pump inhibitors (PPIs). His physical examination was unremarkable. Laboratory tests including whole and routine blood count, liver and thyroid function tests, anti-nuclear antibody, rheumatoid factor and total tryptase levels were normal. Total IgE levels were 46 U/ml. He was prescribed various sedating and nonsedating antihistamines, leukotriene receptor antagonist and anticholinergics. Corticosteroids had a positive effect on urticarial lesions but were ceased due to severe dyspeptic complaints. He underwent an upper gastrointestinal endoscopy and was diagnosed as “eritematous pangastritis.” Histopathological examination revealed minimal to moderate chronic superficial inflammation without activation. Helicobacter pylori infection and “eosinophilic gastritis” were not detected. He was then prescribed different PPIs (lansoprazole and esomeprazole), but, unfortunately, his gastric complaints were not improved. Although using high dose antihistamines and leukotriene antagonists, his CU associated symptoms were not healed. Afterwards, he was prescribed omalizumab 150 mg solution for injection monthly. One month later he was re-evaluated. The life quality of the patient was prominently improved shortly after the first dose, as demonstrated with the dermatologic life quality index,[4] and gastric complaints almost completely disappeared. He is still given omalizumab treatment regularly. He has had minimal skin complaints, only with heavy exercise, during the period when using omalizumab, but no more gastric complaints. Figure 1 Cholinergic urticarial lesions of this 38-year-old male patient. To date, the therapeutic efficacy of omalizumab on CU associated resistant dyspeptic complaints has not been reported. The effectiveness of anti-IgE treatment is not only restricted to inhibition of allergen IgE interactions. It has rather complicated consequences. Stimulation of FceRI in human umbilical cord mast cells causes a substantial change in expression of many genes, including 18 cytokines, 13 chemokines, and several adhesion molecules involved in potential interactions with T cells, B cells, or dendritic cells.[5] It is well-known that the gastrointestinal system plays a central role in immune system homeostasis and its relationship with the immune system is rather complicated. With current information, it is not easy to comment on how this newly emerged multi-potent immune therapeutic agent had these effects on dyspeptic complaints. In conclusion, the therapeutic spectrum of anti-IgE treatment comprises allergic disorders related to many clinical problems, including CU associated dyspeptic complaints.

A successful pregnancy and uncomplicated labor with C1INH concentrate prophylaxis in a patient with hereditary angioedema

Patients with hereditary angioedema (HAE) need a special concern during pregnancy. Although, the disease has a relatively benign course during pregnancy, maternal mortality has been reported. We present a HAE patient with recurrent attacks during pregnancy, but uncomplicated labor under C1INH concentrate prophylaxis.

Chronic urticaria in patients with autoimmune thyroiditis: Significance of severity of thyroid gland inflammation

BACKGROUND There is a clear association between autoimmune thyroiditis (AT) and chronic urticaria/angioedema (CUA). However, not all patients with AT demonstrate urticaria. AIMS The aim of the study was to investigate in which patients with AT did CUA become a problem. A sensitive inflammation marker, neopterine (NP) was used to confirm whether the severity of inflammation in the thyroid gland was responsible for urticaria or not. METHODS Neopterine levels were assessed in patients with AT with urticaria and without urticaria. Furthermore, levels were compared in relation to pre and post levothyroxine treatment. Twenty-seven patients with urticaria (Group 1) and 28 patients without urticaria (Group 2) were enrolled in the study. A course of levothyroxine treatment was given to all patients, and urine neopterine levels before and after the trial were obtained. RESULTS All patients completed the trial. Mean age in Group 1 and Group 2 was similar (35.70 ± 10.86 years and 38.36 ± 10.38 years, respectively) (P=0.358). Pre-treatment urine neopterine levels were significantly higher in Group 1 (P=0.012). Post-treatment levels decreased in each group, as expected. However, the decrease in the neopterine level was insignificant in the patients of Group 2 (P=0.282). In Group 1, a significant decrease in post-treatment neopterine levels (P=0.015) was associated with the remission of urticaria. CONCLUSION In patients with CUA and AT, pre-treatment elevated levels of NP, and its decrease with levothyroxine treatment along with symptomatic relief in urticaria, may be evidence of the relationship between the degree of inflammation in thyroid and presence of urticaria.

Hypersensitivity to aeroallergens in patients with recurrent vulvovaginitis of undetermined etiology

Aim:  Recent findings show that the vaginal mucosa can develop an allergic response to environmental allergens and there is a strong association between atopy and some recurrent vulvovaginal infections. In this study, we investigated prospectively the rate of atopy in patients with recurrent vulvovaginitis of undetermined etiology (RVV).

Efficacy of Omalizumab in a Patient with Angioedema Clinically Resembling a Hereditary Angioedema.

Dear Editor: A 20-year-old man was referred to our allergy and immunology department with complaints of recurring angioedema attacks, lasting 48~96 h, on his lips, eyes, and face, as well as swelling of the extremities and testicles during the last 1 year. Regular use of antihistamine and steroid drugs was generally ineffective against the frequency and severity of the angioedema attacks. He experienced recurrent abdominal pain attacks during the evaluation period. He was hospitalized in another center with a prediagnosis of familial Mediterranean fever; however, that diagnosis was excluded later. Urticarial lesions were not observed during the angioedema attacks. He did not have a history of drug or food allergy, and no specific family history for angioedema was reported. A detailed evaluation for arthritis and rheumatologic disorder was done but no specific findings were found. Furthermore, rheumatologic markers were negative (IRB No. 1491-21-16/1539). Routine laboratory tests for the management of chronic urticaria-angioedema and for anti-nuclear antibody, rheumatoid factor, anti-cyclic citrullinated peptide antibodies, C3, and C4 were within the reference limits. The total immunoglobulin E (IgE) value was 213 IU/ml, and the C4 levels during the attacks were normal. However, C1 esterase inhibitor was measured to be 28.3 mg/dl (reference, 32~39 mg/dl), and hereditary angioedema (HAE) was clinically considered. Danazol treatment up to 400~600 mg/day was started; however, no significant benefit was observed. As the 1,000 U C1 esterase inhibitor administered during the attacks (Cetor, 500 U; Sanquin, Amsterdam, The Netherlands) was ineffective, the diagnosis of HAE was excluded. Because the urticarial complaints started in addition to the angioedema complaints, our patient received 300 mg omalizumab (Xolair 150 mg; Novartis Pharmaceuticals, Basel, Switzerland) subcutaneously every 4 weeks according to conventional asthma treatment protocols. He was treated with omalizumab for 6 months. His angioedema attacks ceased completely within 2 weeks after the start of this treatment. Except for the very short period for the formal procedures required for the procurement of the drug, he had no other complaints during the 6 months follow-up. In randomized, placebo-controlled trials, omalizumab was shown to have excellent efficacy in chronic spontaneous urticaria1. A growing number of case reports and series suggest that anti-IgE treatment may also be beneficial for patients with physical urticarias and chronic angioedema. Recently, omalizumab treatment for inducing and maintaining long-term remission in patients with severe chronic urticaria has been demonstrated2. Unfortunately, for such disorders with complex and unclear etiology, no randomized placebo-controlled trial has been performed yet3. The mechanism of omalizumab activity in angioedema is currently not well defined. However, several mechanism may be considered. Even if the pathogenesis of angioedema in the present case may not be directly mediated by IgE, omalizumab may be effective through an unidentified and indirect anti-inflammatory manner. Sayama et al.4 reported that the stimulation of high-affinity IgE receptor (FceRI) in human umbilical cord mast cells causes substantial change in the expression of many genes, including Interleukin-11 (IL-11), and at least 30 other cytokines and chemokines and several adhesion molecules involved in potential interactions with T cells, B cells, or dendritic cells. Another work, in which the anti-inflammatory activity of omalizumab was mediated, has provided evidence showing the efficacy of this drug in idiopathic angioedema through eosinophil apoptosis induction and downregulation of the inflammatory cytokines IL-2 and IL-135. In conclusion, it seems that therapeutic efficacy spectrum of anti-IgE treatment comprises many allergic disorders with unknown etiology, including angioedema.

Long-Term Omalizumab Treatment: A Multicenter, Real-Life, 5-Year Trial

Background: Omalizumab has demonstrated therapeutic benefits both in controlled clinical trials and real-life studies. However, research concerning the long-term effects and tolerability of omalizumab is needed. The main objective of this study was to evaluate the effectiveness and tolerability of treatment with omalizumab for up to 5 years. Methods: A multicenter, retrospective, chart-based study was carried out to compare documented exacerbations, hospitalizations, systemic steroid requirement, FEV1, and asthma control test (ACT) results during 1 year prior to omalizumab treatment versus at 1, 3, and 5 years of treatment. Adverse events and reasons for discontinuation were also recorded at each time point. Results: Four hundred and sixty-five patients were enrolled in the study. Outcome variables had improved after the 1st year and were sustained after the 3rd and 5th years of treatment with omalizumab. Omalizumab treatment reduced the asthma exacerbation rate by 71.3% (p < 0.001) at 1 year, 64.3% (p < 0.001) at 3 years, and 54.8% (p = 0.002) at 5 years. The hospitalization rate also decreased; by the 5th year of the treatment no patients were hospitalized. ACT results had also improved significantly: 12 (p < 0.001) at 1 year, 12 (p < 0.001) at 3 years, and 12 (p = 0.002) at 5 years. Overall, 12.7% of patients reported adverse events (most of these were mild-to-moderate) and the overall dropout rate was 9.0%. Conclusion: Omalizumab had a significant effect on asthma outcomes and this effect was maintained over 5 years. The drug was found to be generally safe and treatment compliance was good.

Erythrocyte zinc level in patients with atopic dermatitis and its relation to SCORAD index

Introduction Atopic dermatitis (AD) is a chronic, pruritic inflammatory disease, characterized by a relapsing-remitting course. The pathogenesis of atopic dermatitis is not completely understood, although the disorder appears to result from the complex interaction between immune abnormalities, genetic and environmental factors. Trace elements are essential for normal functioning of the immune system. Aim To determine zinc levels in serum and erythrocytes of patients with AD using an atomic absorption spectrometric technique and to investigate the relationship between those levels and disease activity. Material and methods Sixty-seven patients and 49 controls were enrolled into the study. The disease severity of AD patients was determined according to the Scoring Atopic Dermatitis (SCORAD) index. We measured zinc levels in serum and erythrocytes by the atomic absorption spectrophotometric technique. Results Erythrocyte zinc levels were significantly lower in AD patients than in the control group (p < 0.001), whereas serum zinc levels did not differ between the groups (p = 0.148). In the AD patient group there was a negative correlation between the SCORAD score and erythrocyte zinc levels (r = –0.791; p < 0.001). Conclusions The negative relationship between disease severity and erythrocyte zinc levels might suggest an immunopathological link between AD progression and intracellular zinc metabolism.