The Turkish Hereditary Angioedema Pilot Study (TURHAPS): the first Turkish series of hereditary angioedema.

BACKGROUND: No published data presently exist concerning hereditary angioedema (HAE) in Turkey. The aim of the study was to initiate a preliminary multicentric evaluation about HAE and to determine the genetic properties of Turkish patients. METHODS: Based on records drawn from four medical centers we identified a total of 70 subjects, belonging to 60 unrelated families, fulfilling clinical and laboratory criteria for diagnosis of HAE with C1 inhibitor deficiency. Ten type I patients, and their first-degree relatives, underwent genetic analysis for HAE. RESULTS: The majority of patients were female (60%), the mean age was 37.7 ± 14.1 years. The mean age at the time of first angioedema symptom was 12.5 ± 9.2 years. Mean time lag between first symptom and diagnosis was 26 ± 14.4 years. All but 3 subjects had HAE type I. Family history of angioedema was present in 75.7% of the cases. Cutaneous swelling was reported by 87.1% of the patients, facial edema by 65%, abdominal symptoms by 74.3% and approximately one half (55.7%) had experienced one or more laryngeal attack. Genetic analysis of 10 families demonstrated that 5 carried a mutation that had never been previously described. CONCLUSION: We found that the clinical features of Turkish HAE patients were consistent with previously described patterns of this rare disease. The most noteworthy feature identified in the study was a significantly long duration between the first symptom appearance and final diagnosis. Our detection of different mutations in 10 patients confirms the allelic heterogeneity of the disease.

Neurotrophins: are they meaningful in chronic spontaneous urticaria?

Plasma neurotrophin levels are elevated in patients with allergic and autoimmune diseases. The present study was designed to investigate the serum neurotrophin levels in 42 patients displaying chronic spontaneous urticaria, as well as 22 healthy control subjects. Blood samples were obtained from subjects during their first visit to the clinic, and then again after one month of desloratadine therapy. No significant difference was found between patient and control groups in terms of basal serum neurotrophin levels. However, basal nerve growth factor levels in patients whose symptoms persisted despite treatment were significantly lower than those of the drug-responsive patients and the control group. In treatment-responsive patients, nerve growth factor increased after suppression of the symptoms. Our study suggests that chronic spontaneous urticaria is linked with changes serum nerve growth factor levels, and that the deregulation of neurotrophins may contribute to urticaria pathophysiology.

Recurrent anaphylaxis due to non-ruptured hepatic hydatid cysts.

BACKGROUND: Hydatid disease, a parasitic infestation of humans, is endemic in the Mediterranean region, Australia, New Zealand and the Middle East, and mostly involves the liver. Anaphylactic reactions, which sometimes are the first manifestations of the disease, frequently occur due to cyst rupture after a minor/major trauma, though they may also be spontaneously seen on rare occasions. In extremely few studies, anaphylactic shock has been reported in patients without macroscopic rupture of the hydatid cysts. CASE REPORT: Our patient had recurrent anaphylactic episodes without any trauma and had been misdiagnosed for several years even though the patient was living in a region endemic for hydatid disease. CONCLUSION: We emphasize that physicians should be highly aware of hydatid disease as a possible etiology for seemingly idiopathic anaphylactic reactions, especially in endemic regions.

Serum amyloid A (SAA) in induced sputum of asthmatics: a new look to an old marker.

BACKGROUND: Some cellular and soluble markers of inflammation in induced sputum have been used for studying airway inflammation in asthma. The aim of this study was to assess the usefulness of systemic inflammation marker serum amyloid A (SAA) in blood and induced sputum to monitor the airway inflammation in asthmatic patients. METHOD: Seventeen non-smokers newly diagnosed mild to moderate asthmatic patients and 10 healthy volunteers were included in this prospective parallel designed study. Inflammatory cell counts, SAA and eosinophil cationic protein (ECP) levels were measured in sera and induced sputum of both groups. All tests were repeated in the asthma group after 6 months of inhaled steroid therapy. The diagnostic accuracy and reproducibility of sputum and blood SAA were estimated. RESULTS: Serum and induced sputum SAA and ECP levels, sputum eosinophils and neutrophils of untreated asthmatic patients were significantly greater compared to the control group. Sputum and sera SAA levels and sputum neutrophils remained unchanged after the 6 months of anti-inflammatory therapy, although ECP levels, sputum eosinophils and macrophages were significantly reduced. The area under the curve (AUC) for sputum SAA was found equal to AUC for sputum ECP (0.87). The reproducibility of sputum SAA was satisfactory (ICC=0.84) as well. CONCLUSION: Our findings suggest that systemic inflammatory marker SAA may be used as a reliable inflammatory marker in asthma. The facts that whether it remarks an ongoing inflammation unresponsive to treatment in the airways or reflects a systemic inflammation needs to be clarified with further studies.

Nigella sativa (black seed) oil does not affect the T-helper 1 and T-helper 2 type cytokine production from splenic mononuclear cells in allergen sensitized mice.

Nigella sativa Linn. (Ranunculaceae) is known to have beneficial effects on a wide range of diseases including asthma. However, the mechanism of action in asthma and other allergic diseases is not entirely clear. The present study was planned to evaluate the effects of Nigella sativa on cytokine production of splenic mononuclear cells in ova-sensitized mice. Nineteen two-month-old BALB/c mice were given 0.3 mL of Nigella sativa oil by oro-eosophageal cannula once a day for a month. The control group consisting of 10 mice took 0.3 mL of 0.9% saline solution by the same route for the same period. In the third week of the study, all mice were sensitized by means of intraperitoneal injections of 20 microg of ovalbumin (OVA-Grade VI, Sigma). Ova injections were repeated three times with 7-day intervals. After another week, all mice were sacrificed by means of cervical dislocation. Then the splenic mononuclear cells (MNCs) of mice were cultured with OVA or Concavalin A (Con-A). From the culture supernatants, IL-4, IL-10 and IFN-gamma were assessed by means of ELISA. The cytokine production of splenic MNCs of mice that were given Nigella sativa for 30 days was not significantly different than those who took saline solution instead. In conclusion, Nigella sativa oil seems not to have an immunomodulatory effect on Th1 and Th2 cell responsiveness to allergen stimulation.

Effects of SiO2 in Turkish natural stones on cancer development.

In materials science, one of the new concerns in the construction industry, it is well established that mineral dust from rocks (stones) has adverse effects on human health. For instance, it is suspected that some mineral dusts in particular leads to occupational diseases, including lung cancer. The present research concerned the relationship between cancer and those workers who work in Turkish construction industry and quarries and are exposed to silica mineral dust from natural stones. One focus was cancer prevention methods applied in-site. In mining and construction industry where stone dust is widely used, silicosis induced lung cancer is frequently seen. Cancer cases which are seen across the regions mostly affected by silica containing dust in Turkey were identified and a survey was conducted of the methods to protect workers in the construction industry from exposure to silica dust.

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 H(1) 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.

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.

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.

Latex sublingual immunotherapy: can its safety be predicted?

BACKGROUND: Complete avoidance sometimes cannot be possible in latex-allergic health care workers. So far, very few double-blind placebo-controlled studies revealed the efficacy of sublingual latex immunotherapy (SLIT) in those patients. OBJECTIVE: Our aim was to evaluate the efficacy and safety of latex SLIT in health care workers. METHODS: 30 patients (all health care workers) diagnosed as latex allergic were advised to avoid latex exposure and were given information about the prevention measures and asked to return two months later. 24 patients who were still symptomatic despite prevention measures were informed about the latex SLIT study and asked to participate. However, only 12 gave approval and were randomized to receive sublingual latex extract or placebo. Symptom scores and latex cutaneous provocation test scores were recorded at baseline and at the 6th and 12th months of the study. RESULTS: Two patients experienced anaphylaxis, 1 patient showed severe bronchial obstruction during dose incremental phase and were excluded from the study. The differences of the symptom and provocation scores between baseline and the 12th month of the treatment were significant in the active group (p = .042, p = .038, respectively). Also the symptom and provocation scores at 12 months were significantly lower in the active group than in the placebo group (p = .035, p = .013, respectively). CONCLUSION: Latex SLIT can be used as an effective treatment for latex-allergic health care patients having difficulties in applying adequate avoidance measures. However, the risk of systemic reactions should be kept in mind and sufficient precaution measures must be made available.

Allergic vs nonallergic rhinitis: which is more predisposing to chronic rhinosinusitis?

BACKGROUND: The impact of allergy on chronic rhinosinusitis (CRS) is controversial. OBJECTIVE: To evaluate whether a history of CRS is more prevalent in patients with allergic rhinitis than in those with nonallergic persistent rhinitis. METHODS: A total of 115 patients (78 females; mean age, 31.9 years; age range, 14-64 years) with persistent rhinitis were included in the study. A 7-point analog scale was used to report the severity of individual and global CRS symptoms and to determine the impact of rhinosinusitis symptoms on quality of life. The allergic status of the patients was evaluated using skin prick tests for common inhalant allergens, and asthma was evaluated by means of history, physical examination, and respiratory function tests. Rhinoscopy and paranasal sinus computed tomography were used to determine CRS. RESULTS: Asthma and CRS were not significantly different in allergic and nonallergic patients. Nasal polyps were found equally in both groups (8 patients). However, mean Lund-Mackay staging scores, postnasal drainage, dental pain, and global CRS scores were significantly higher in patients with nonallergic rhinitis (P = .045, P = .001, P = .02, and P = .01, respectively). No significant correlations, except for dental pain (correlation coefficient, 0.250; P = .008), were found between Lund-Mackay scores and CRS symptoms. In rhinoscopy, the only conspicuous difference was nasal purulence in allergic patients (P = .002). CONCLUSION: Allergic and nonallergic rhinitis may contribute similarly to the development of CRS.

Acute phase reactants in allergic airway disease.

Acute phase reactants have been implicated for their involvement as proinflammatory molecules in various inflammatory diseases. However, little is known regarding their role in the allergic airway disease. The aim of the present study was to examine the blood concentrations of three acute-phase proteins, namely C-reactive protein (CRP), serum amyloid A (SAA) and fibrinogen in patients with allergic rhinitis and asthma. Three study groups include: non-smoker allergic rhinitis (n = 50), non-smoker asthma (n = 20), and non-allergic, non-smoker healthy control subjects (n = 20). Patients who have had recent upper or lower respiratory tract infection and trauma, any rheumatological illnesses, malignancy or obesity were excluded. Blood samples were obtained from all the patients and control subjects and were analyzed for serum CRP, SAA and plasma fibrinogen. The mean CRP and fibrinogen values in the rhinitis and asthma groups were not significantly different when compared to the control group. However, the mean SAA levels of both groups were found to be significantly higher than those of the control group (p = 0.002 for rhinitis, p = 0.02 for asthma). There was no significant correlation between the FEV(1) values and the levels of the serum markers. This study demonstrates that acute phase reactant SAA rises in patients with allergic rhinitis and patients with asthma. We therefore suggest that SAA may have a role in the inflammatory airway disease.