Mustafa Demirtürk

Omalizumab markedly improves urticaria activity scores and quality of life scores in chronic spontaneous urticaria patients: A real life survey

Treatment of chronic urticaria consists of antihistamines as the first‐line treatment. For more severe symptoms, combinations can be necessary as well as dose augmentations. The recent guidelines suggest the possibility of using omalizumab in resistant cases, but this therapy is still investigational. We treated two patients with idiopathic recurrent angioedema and 12 patients with chronic spontaneous urticaria (CSU) with omalizumab, who had not benefited from the recommended first‐line, second‐line and third‐line treatments. To evaluate the efficacy of the omalizumab treatment, urticaria activity scores (UAS) and chronic urticaria quality of life (CU‐Q2oL) scores were measured at baseline, and at the end of the first and sixth month of the therapy. The dosage and intervals of omalizumab therapy were determined according to the rules suggested for severe asthma treatment. CU‐Q2oL scores and UAS displayed significant improvements in all 14 patients. None of the patients reported any adverse effect during the treatment until the submission of this data. Our results show that omalizumab apparently improves CU‐Q2oL as well as UAS in treatment‐resistant CSU in a real life setting.

Coronary artery calcification and coronary flow velocity in haemodialysis patients

BACKGROUND Decreased coronary flow reserve (CFR) is a marker of endothelial dysfunction, coronary artery calcification and inflammation, well-known cardiovascular risk factors in haemodialysis (HD) patients. In this study, we aimed to investigate the correlation of coronary artery calcification scores (CACS) with CFR in HD patients. METHODS Sixty-four end-stage renal failure patients were enrolled in this study (38 males, 26 females). Thirty-nine healthy subjects (22 males, 17 females) were included in the control group. Biochemical parameters and acute-phase inflammation marker [high-sensitivity C-reactive protein (hs-CRP)] of patients were recorded before dialysis. The CACS were measured by electron beam computerized tomography method. CFR recordings were performed by trans-thoracic Doppler echocardiography. The relationship between CACS and CFR was evaluated. RESULTS The mean CACS was 281 +/- 589 and 29 patients had CACS < 10. Patients with CACS > 10 had significantly lower CFR values compared to patients with CACS < 10 (1.56 +/- 0.38 vs 1.84 +/- 0.53, P = 0.024). However, there was no difference in hs-CRP values between the groups. CFR was negatively correlated with CACS (r = -0.276, P = 0.030). In multiple stepwise regression analysis, CACS was found to be an independent variable for predicting CFR (P = 0.048). During a follow-up of 18 months, 10 patients had experience of cardiovascular events. Patients with CACS > 10 had significantly higher event rate [34.5% (10/29) vs 0% (0/24)] compared to those with CACS < 10 (P = 0.001). Patients who developed cardiovascular events had significantly higher mean CACS and lower CFR values than the remaining group (P = 0.019 and P = 0.039). All of four patients who died during follow-up were in the CFR < 2 and CACS > 10 groups. CONCLUSIONS CACS was associated with CFR in HD patients. However, we did not find any association of inflammation with CACS and CFR. This association between CFR and CACS might indicate two different (anatomical and functional) aspects of the common pathophysiology of the arterial system in HD patients.

Coronary flow reserve dysfunction in hemodialysis and kidney transplant patients

Abstract: Background:  The assessment of coronary flow reserve (CFR) by trans‐thoracic echocardiography has recently been introduced into clinical studies. Impairment of coronary microvascular functions and decreased CFR detected by trans‐thoracic Doppler harmonic echocardiography (TTDE) has recently been reported in hemodialysis (HD) patients, but there is no comparative study between HD patients and renal transplant recipients.

Promising option in the prevention of idiopathic anaphylaxis: omalizumab.

Anaphylaxis is a serious and probably lethal systemic reaction which occurs instantaneously after exposure to an allergen. It can occur after exposure to various triggers including allergic and non‐allergic factors. When a trigger cannot be determined, idiopathic anaphylaxis is considered. In idiopathic anaphylaxis presenting with frequent attacks, long‐term prophylaxis with H1 antihistamine and steroid treatment are recommended. Omalizumab, a humanized monoclonal antibody drug which decreases free immunoglobulin E molecules in the circulation, is approved for the treatment of chronic severe persistent allergic asthma. We report a 46‐year‐old female patient with severe uncontrolled allergic asthma and idiopathic anaphylaxis presenting with attacks of abdominal pain, generalized urticaria, feeling of strangulation in her throat and unconsciousness. Omalizumab at a dose of 375 mg once every 2 weeks was administrated and at the end of 3 months anaphylactic attacks had ceased. At the end of the sixth month of omalizumab therapy, her injection intervals were extended to 4 weeks. After she began experiencing moderate attacks of urticaria and hoarsening, however, initial treatment plan was reestablished. Currently, she has completed her first year of treatment without further attacks.

Coronary flow reserve is impaired in patients with adult growth hormone (GH) deficiency

Objective  Relationship between adult growth hormone deficiency (AGHD) and increased cardiovascular disease risk is very well known in hypopituitary patients treated with conventional hormone replacement therapy other than growth hormone (GH) administration. Endothelial dysfunction, an early and reversible event in pathogenesis of atherosclerosis, is associated with increased vascular smooth muscle tone, arterial stiffening and intima‐media thickness (IMT). Coronary flow reserve (CFR) measurement by transthoracic Doppler echocardiography (TTDE) reflects coronary microvascular and endothelial functions, as a cheaper and an easy screening test. We have used TTDE to evaluate endothelial function and coronary microvascular function in AGHD.

Oral nickel exposure may induce Type I hypersensitivity reaction in nickel-sensitized subjects.

BACKGROUND Little is known about the clinical and immunological changes in the nickel allergic patients with systemic symptoms. We aimed to evaluate T helper cell responses of patients with different clinical presentations due to nickel. METHODS Patients having various allergic symptoms and positive patch test results to nickel and 20 controls underwent skin prick tests with nickel. IL-10, IL-4, IL-5 and IFN-gamma were measured in the culture supernatants of PBMC stimulated by nickel during lymphocyte proliferation test (LTT). RESULTS 69 patients (56 female, mean age: 49.2 ± 13.1), 97% having nickel containing dental devices and 20 controls (8 female, mean age 34.9 ± 12.06) were evaluated. Skin prick tests with nickel were positive in 70% of the patients (p<0.001), being significantly higher in the patients with urticaria/angioedema (p=0.02). The LTT stimulation index (p<0.0001), IL-4 (p=0.002), IFN-gamma (p=0.01), IL-5 (p=0.04) and IL-10 (p=0.003) were higher in the patient group. LTT stimulation index, IL-4 and IL-10 were significantly elevated in patients having urticaria, angioedema and respiratory symptoms when compared to those who had only oral symptoms or systemic dermatitis (p=0.004, p=0.002 and p=0.01, respectively). CONCLUSION This study suggests the presence of Type I hypersensitivity in addition to a Type IV immune reaction in patients with chronic systemic symptoms related to nickel. Nickel containing dental alloys and oral nickel intake seem to trigger systemic symptoms in previously nickel sensitized patients.

Increased eNOS levels in hereditary angioedema.

BACKGROUND Hereditary angio-edema (HAE), characterized by recurrent episodes of angioedema involving the skin and the mucosa of the upper respiratory or the gastrointestinal tracts, results from heterozygosity for deficiency of the serine proteinase inhibitor (serpin), C1 inhibitor (C1-INH). OBJECTIVE In this study, serum inflammatory cytokine levels and circulating endothelial cells collected from HAE patients during both acute attacks and asymptomatic periods were evaluated. METHOD Twenty-four patients with Type I and 1 patient with Type II HAE in an asymptomatic period (Group I), 8 patients with Type I HAE during a mild to moderate acute attack (Group II) and 20 healthy subjects (13 females, mean age: 32.1±8.2years) were included. Serum IL-6, IL-8, IL-1β, TNF-α, vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) levels were detected by ELISA. Circulating endothelial cells (CECs) and circulating endothelial progenitors (CEPs) were evaluated using Fluorescence Activated Cell Sorting (FACS). RESULTS Serum eNOS levels of HAE patients were significantly higher than healthy subjects (p<0.006) while mean TNF-α levels in Group I were slightly lower (p<0.03) than Group II. There were no differences in terms of other inflammatory cytokines between the control subjects and HAE patients who were either in an asymptomatic period or experiencing an acute attack. CECs and CEPs were also similar. CONCLUSION These results suggest that an inflammatory response is not necessary to trigger HAE attacks. On the other hand, increased eNOS levels might reflect a sustained hyperpermeability state in HAE patients.

There is an increased risk of atherosclerosis in hereditary angioedema.

BACKGROUND Hereditary angioedema is associated either with a deficiency in the amount or in the function of the C1 inhibitor (C1 INH). OBJECTIVE In this study the endothelial function of HAE patients was investigated to evaluate the impact of hereditary C1-INH deficiency on atherosclerosis, which has not yet been established before. METHODS A total of 26 patients (14 female, 12 male. Mean age: 38±13) diagnosed with HAE and 30 healthy controls were enrolled in the study. Measurement of coronary flow reserve (CFR) in the left anterior descending coronary artery was performed using transthoracic doppler harmonic echocardiography at baseline and following dipyridamol infusion. The intima-media thickness (IMT) in the carotid artery was measured using an echocardiographic system equipped with 10 MHz linear transducer (Vingmed System Five). RESULTS The mean CFR value for the HAE patient group was significantly lower than that of the control group (p<0.001). The mean IMT was not found to be significantly different between the two groups, although it was slightly higher in the HAE patient group. No correlation was found between the CFR and the disease severity scores, nor was it shown between the CFR values and the duration of danazol treatment. CONCLUSION Our results indicate that there is a microvascular endothelial dysfunction in HAE patients. Although carotid intima media thickness of these patients was not significantly increased, the presence of microvascular endothelial dysfunction might be regarded as an early indicator of a premature atherosclerosis.

Nickel dental alloys can induce laryngeal edema attacks: A case report

Nickel is a strong immunological sensitizer and may result in contact hypersensitivity. Case reports of allergic reactions to intraoral nickel have occasionally been reported in the published work and these allergic reactions are generally of a delayed type (type IV). Here, we present a case of a nickel allergic patient displaying frequent laryngeal edema attacks which required treatment with epinephrine injections followed by parenteral corticosteroid doses. Her complaints ceased after the removal of the dental bridge and the foods containing nickel. In summary, we propose that in the case of recurrent laryngeal edema attacks without any explainable cause, an allergic reaction due to nickel exposure should be taken into consideration.

The importance of mold sensitivity in nonallergic rhinitis patients

In recent studies, local specific immunoglobulin E (sIgE) production against allergens in nasal mucosa and a positive response to a nasal allergen provocation test (NAPT) have been demonstrated in some patients initially diagnosed as nonallergic rhinitis (NAR) or idiopathic rhinitis (IR). The aim of this study was to evaluate the presence of local allergic rhinitis (LAR) in patients who experience rhinitis symptoms in indoor and outdoor moldy conditions and to investigate the role of the NAPT in diagnosis.