Comparison of recent anaphylaxis diagnostic criteria in real life: Can more patients be diagnosed as having anaphylaxis?

Introduction: In 2020, World Allergy Organization (WAO) updated their diagnostic criteria for anaphylaxis, which differed as a result from the National Institute of Allergy and Infectious Diseases/Food Allergy and Anaphylaxis Network (NIAID/FAAN) criteria which were still used in the 2021 update of the European Academy of Allergy and Clinical Immunology (EAACI) anaphylaxis guideline. Our aim was to evaluate and to compare both diagnostic criteria and attempt to identify factors affecting severity of anaphylaxis. Methods: The medical records of the patients who were evaluated with suspected anaphylaxis at 3 medical centers in Türkiye between 2014 and 2021, and underwent a detailed diagnostic work-up, were analyzed retrospectively. Diagnosis of anaphylaxis was evaluated based on the WAO 2020 and EAACI 2021 and NIAID/FAAN diagnostic criteria. The severity of anaphylaxis was determined according to the WAO systemic allergic reaction grading system. Grade 5 anaphylaxis was defined as having respiratory failure, collapse/hypotension, loss of consciousness. Patients' demographic and clinical characteristics were further analyzed depending on the severity of the reaction. Results: One thousand and six patients were evaluated and 232 patients without a convincing diagnosis of anaphylaxis were excluded from the study. The remaining 774 patients (70.6% female, median [Inter quartile range (IQR) 25-75] age: 42 [33-52]) were included for further examination. Anaphylaxis was diagnosed in 729 (94.2%) patients meeting both criteria whereas 35 patients (4.5%) with isolated laryngeal involvement and 10 (1.3%) patients with isolated respiratory involvement were only diagnosed according to the WAO 2020 criteria. Twenty-three patients (3.0%) had a diagnosis of indolent systemic mastocytosis. Mastocytosis was related to grade 5 anaphylaxis [p = 0.022, OR (CI) = 2.9 (1.1-7.6)]. Venom allergy was a risk factor for grade 5 anaphylaxis among those for whom an eliciting allergen could be determined [p = 0.03, OR (CI) = 2.7 (1.1-6.8)]. For drug induced anaphylaxis, parenteral route of drug administration and proton pump inhibitor (PPI) allergy were considered as risk factors for grade 5 anaphylaxis [p < 0.001, OR (CI) = 6.5 (2.5-17.0); p = 0.011, OR (CI) = 10.3 (1.6-63.3)]. Conclusion: This multicenter study demonstrated that both criteria identified the majority of patients with anaphylaxis, but the WAO 2020 diagnostic criteria identified an additional 6%. Hymenoptera stings, PPI allergy, parenteral drug administration, and underlying mastocytosis were associated with more severe episodes.

Urticaria exacerbations and adverse reactions in patients with chronic urticaria receiving COVID-19 vaccination: Results of the UCARE COVAC-CU study.

BACKGROUND: Concern about disease exacerbations and fear of reactions after coronavirus disease 2019 (COVID-19) vaccinations are common in chronic urticaria (CU) patients and may lead to vaccine hesitancy. OBJECTIVE: We assessed the frequency and risk factors of CU exacerbation and adverse reactions in CU patients after COVID-19 vaccination. METHODS: COVAC-CU is an international multicenter study of Urticaria Centers of Reference and Excellence (UCAREs) that retrospectively evaluated the effects of COVID-19 vaccination in CU patients aged ≥18 years and vaccinated with ≥1 dose of any COVID-19 vaccine. We evaluated CU exacerbations and severe allergic reactions as well as other adverse events associated with COVID-19 vaccinations and their association with various CU parameters. RESULTS: Across 2769 COVID-19-vaccinated CU patients, most (90%) received at least 2 COVID-19 vaccine doses, and most patients received CU treatment and had well-controlled disease. The rate of COVID-19 vaccination-induced CU exacerbation was 9%. Of 223 patients with CU exacerbation after the first dose, 53.4% experienced recurrence of CU exacerbation after the second dose. CU exacerbation most often started <48 hours after vaccination (59.2%), lasted for a few weeks or less (70%), and was treated mainly with antihistamines (70.3%). Factors that increased the risk for COVID-19 vaccination-induced CU exacerbation included female sex, disease duration shorter than 24 months, having chronic spontaneous versus inducible urticaria, receipt of adenovirus viral vector vaccine, having nonsteroidal anti-inflammatory drug/aspirin intolerance, and having concerns about getting vaccinated; receiving omalizumab treatment and Latino/Hispanic ethnicity lowered the risk. First-dose vaccine-related adverse effects, most commonly local reactions, fever, fatigue, and muscle pain, were reported by 43.5% of CU patients. Seven patients reported severe allergic reactions. CONCLUSIONS: COVID-19 vaccination leads to disease exacerbation in only a small number of CU patients and is generally well tolerated.

Comparison of 300 mg versus 600 mg daily maintenance doses of aspirin treatment after desensitization in N-ERD: A three-year multicentre experience.

Background: Aspirin treatment after desensitization (ATAD) is effective in preventing nasal polyps recurrence as well as respiratory symptoms in patients with nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory diseases (N-ERD). However, there is no consensus on effective daily maintenance doses in ATAD. Therefore, we aimed to compare the effects of two different maintenance doses of aspirin on clinical outcomes for 1-3 years of ATAD. Methods: This was a retrospective, multicenter study that involved four tertiary centers. The maintenance doses of daily aspirin were 300 mg in one center and 600 mg in the remaining three. The data of patients who were on ATAD for 1-3 years were included. Study outcomes (nasal surgeries, sinusitis, asthma attacks, hospitalization, oral corticosteroid use, and medication uses) were assessed in a standardized way and recorded from case files. Results: The study initially included 125 subjects, 38 and 87 were receiving 300 and 600 mg daily aspirin for ATAD, respectively. Number of nasal polyp surgeries decreased after 1 -3 years compared with before ATAD in both groups (group 1, baseline: 0.44 ± 0.07 versus first year: 0.08 ± 0.05; p < 0.001 and baseline: 0.44 ± 0.07 versus 3rd year: 0.01 ± 0.01; p < 0.001; and group 2, baseline 0.42 ± 0.03 versus first year: 0.02 ± 0.02; p < 0.001 and baseline: 0.42 ± 0.03 versus 3rd year: 0.07 ± 0.03; p < 0.001). Conclusion: Given the comparable effects of 300 mg and 600 mg aspirin daily as maintenance treatment of ATAD on both asthma and sinonasal outcomes in N-ERD, our results suggest using 300 mg of aspirin daily in ATAD owing to its better safety profile.

Comprehensive mastocytosis data analysis from a single center.

Mastocytosis is a very rare disorder and is divided into three prognostically distinct variants by World Health Organization: Cutaneous mastocytosis (CM), systemic mastocytosis (SM), and mast cell sarcoma or localized mast cell (MC) tumors. The wide range of complaints may cause patients to consult various clinics, with resulting mis- or underdiagnosis. Therefore, cooperation between different subspecialties is of paramount importance. In this article, we have compiled 104 adult mastocytosis cases diagnosed and followed in our Hematology and other clinics. 86 (82.7%) of 104 patients had systemic mastocytosis. Osteoporosis, disease-related complications, and secondary malignancies are important topics in this group. We know that indolent form has great survival. But smoldering or aggressive mastocytosis has a poor prognosis. CM and indolent SM have a significantly better prognosis compared to aggressive SM (p < 0.001). We found that the presence of more than 25% of mast cells in the bone marrow, the presence of concomitant marrow dysplasia, and the presence of disease-related complications affect survival (p < 0.001). In addition to the WHO classification, the IPSM scoring system is indicative of the prognosis in this rare disease.

Anaphylaxis in Risky Populations.

Anaphylaxis should be clinically diagnosed with immediate recognition, whereas, despite advances in the field of allergy, the symptoms of anaphylaxis remain to be under-recognized, diagnosis is often missed, and treatment is often delayed. Anaphylaxis presents with symptoms in a spectrum of severity, ranging from mild objective breathing problems to circulatory shock and/or collapse. Indeed, anaphylaxis management frequently relies on a 'one-size-fits-all approach' rather than a precision medicine care model, despite the evidence that anaphylaxis is a heterogeneous condition with differences in causative agents, clinical presentation, and host susceptibility. The key important risk factors for severe anaphylaxis and mortality are certain age groups or certain stages of life (infants, elderly and pregnant women), augmenting factors (physical exercise, alcohol consumption, menstruation, acute infections), concurrent use of some medications (beta-adrenergic blockers (ß-blockers) and angiotensin-converting enzyme (ACE) inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), and proton pump inhibitors (PPIs), and concomitant diseases (i.e. asthma, cardiovascular disease, mastocytosis). The present review aims to collectively address the patient groups who are at high risk of having anaphylaxis, those who have a more severe course, those that are difficult to diagnose, and require a special approach in treatment. Therefore, the risky populations like the elderly, pregnant women, patients receiving ß- blockers or ACE inhibitors, those with concomitant cardiovascular diseases, asthma, and mastocytosis, or those having higher baseline serum tryptase levels are discussed, including their clinical presentations and treatment strategies. Additionally, anaphylaxis during the perioperative period is addressed.

Evaluation of oxidative stress biomarkers and antioxidant parameters in allergic asthma patients with different level of asthma control.

OBJECTIVE: There is evidence that reactive oxygen species, especially free radicals, produced during the immune and inflammatory response may play important roles in the development of asthma.We aimed to evaluate the levels of certain oxidative stress biomarkers and antioxidant capacity in asthma patients with different asthma control levels in comparison to healthy subjects. METHODS: A total of 120 adult allergic asthma patients and 120 healthy individuals were included in this study. Using spectrophotometric methods, we analyzed two oxidative stress markers, levels of malondialdehyde (MDA) and protein carbonyls (PC), as well as reduced glutathione (GSH), total antioxidant capacity (FRAP) and catalase activity as critical antioxidant defense parameters in the blood samples of allergic asthma patients and healthy controls. The patients were divided into 3 subgroups according to asthma control test (ACT) results: totally controlled (TCG), partially controlled (PCG) and uncontrolled (UCG) subgroups. All biomarkers were compared between the three patient subgroups, as well as between total asthma patients and control subjects. RESULTS: There were remarkable differences between the control group and the combined patient group for all parameters. A significant increase in MDA and PC, especially in the UCG (p < 0.01 and p < 0.05, respectively) was detected in comparison to other subgroups. Additionally, increased MDA and PC levels, as well as decreased GSH levels were observed in all subgroups individually in comparison to the control (p < 0.001). CONCLUSIONS: This research demonstrates the presence of severe oxidative stress, considering the increase in lipid peroxidation and protein oxidation, in patients with allergic asthma, even under controlled conditions.

Impact of mental health on disease activity in mastocytosis during COVID-19 pandemic.

BACKGROUND: Mast cell-related symptoms might be influenced by mental health status in mastocytosis. In this study, we aimed to investigate the influence of mental health problems developed during the COVID-19 pandemic on the course of mastocytosis. METHODS: Mental health status in 60 adult patients with mastocytosis was prospectively evaluated with the total Depression-Anxiety-Stress Scale (tDASS-21) and Fear of COVID-19 Scale (FCV-19S) in the lockdown period (LP) and the return to normal period (RTNP) during the pandemic. The disease course was assessed from emergency and outpatient medical reports, including Scoring Mastocytosis (SCORMA) index and serum baseline tryptase levels, by telephone interviews and clinical visits. RESULTS: The mean FCV-19S and median tDASS-21 scores were significantly higher in LP than RTNP (p < 0.001) and there was a positive correlation between FCV-19S and tDASS-21 in LP (r = 0.820, p < 0.001) and in RTNP (r = 0.572 p= <0.001). Disease-related symptoms including skin lesions, flushing and anaphylaxis attacks increased in 22 patients in LP, and in this group, mean FCV-19S and median tDASS-21 were higher than those without symptom exacerbation (p < 0.001). During the study period, four (6.7%) patients who experienced COVID-19 recovered without any requirement for hospitalization and had not experienced symptom exacerbation. CONCLUSIONS: Fear of COVID-19 can be a reason for mental health changes, including depression, anxiety and stress which may further increase mast cell-related symptoms. Therefore, psychological support is important to control the severity of mast cell-related symptoms in mastocytosis during a pandemic.

Paucigranulocytic asthma: Do sputum macrophages matter?

Background: Although paucigranulocytic asthma (PGA) is the most common phenotype of stable asthma, its features have not been adequately studied. In this study, we aimed to display the characteristics of PGA. Method: A total of 116 non-smoking adult patients with asthma (80% women; mean ± standard deviation age, 39 ± 12.9 years) admitted to three tertiary centers were included. Their demographic and clinical features, allergy status, biochemical results, scores of Asthma Control Test (ACT), spirometry, and exhaled nitric oxide (FeNO) measurements were obtained. Induced sputum cytometry was performed. Results: Four phenotypes, according to induced sputum cell counts, were detected: eosinophilic asthma (EA) (22.4%), mixed granulocytic asthma (MGA) (6.9%), neutrophilic (NA) (7.8%), and PGA (62.9%). In the sputum, macrophages were higher in the PGA group compared with the other groups (PGA versus NA and PGA versus MGA, p < 0.001; and PGA versus EA, p =0 .030). The atopy rate between phenotypes was the same. Although the forced expiratory volume in the first second of expiration (FEV1) was similar in four groups, the ratio of FEV1 to the forced vital capacity ratio was higher (p = 0.013) and FEV1 reversibility was lower in the patients with PGA than the corresponding values in other phenotypes (p = 0.015). Low reversibility was comparable both in patients with PGA who were inhaled corticosteroid (ICS) naive and in patients on ICS treatment. Although insignificant, the FeNO values and blood eosinophil counts were higher in the MGA and EA groups, whereas these were the lowest in the PGA group. The uncontrolled asthma ratio was low in PGA (16%), whereas it was 11% for NA, 25% for MG, and 23% in EA. Conclusion: Macrophages are predominant in sputum of patients with PGA. Besides a lower uncontrolled asthma ratio, lower FEV1 reversibility is a prominent characteristic of this phenotype.

Impaired endothelial function irrespective of systemic inflammation or atherosclerosis in mastocytosis.

BACKGROUND: Knowledge on endothelial dysfunction and its relation to atherosclerosis in mastocytosis is limited. OBJECTIVE: To investigate the endothelial function in mastocytosis by flow-mediated dilatation (FMD) and biomarkers related to vascular endothelia and to evaluate its relationship with the presence of subclinical atherosclerosis by carotid intima media thickness (CIMT). METHODS: A total of 49 patients with mastocytosis and 25 healthy controls (HCs) were included. The FMD and CIMT during transthoracic echocardiography biomarkers including endocan, endothelin-1, and vascular endothelial growth factor (VEGF) were measured in the sera of participants. Tumor necrosis factor-alpha, interleukin 6, and high-sensitive C-reactive protein were determined as inflammatory biomarkers. RESULTS: The mean FMD % was lower in the patients than HCs (11.26% ± 5.85% vs 17.84% ± 5.27% P < .001) and was the lowest in the advanced systemic mastocytosis and smoldering systemic mastocytosis group among the patients (P = .03). The median value of VEGF was considerably higher in patients than HCs (73.30 pg/mL; minimum-maximum 32.46-295.29 pg/mL vs 46.64 pg/mL; minimum-maximum, 11.09-99.86 pg/mL; P = .001) and it was the highest in the advanced systemic mastocytosis and smoldering systemic mastocytosis group (P = .01). The FMD was inversely correlated with endocan (r = -0.390; P = .006), endothelin-1 (r = -0.363; P = .01) and VEGF (r = -0.402; P = .004) but there were no correlations between FMD and tumor necrosis factor-alpha, interleukin 6, and high-sensitive C-reactive protein. No differences in CIMT values between patients and HCs and no correlation between CIMT and the biomarkers were observed. CONCLUSION: Endothelial dysfunction in mastocytosis becomes evident with decreased FMD and elevated serum VEGF in the absence of atherosclerosis or systemic inflammation and is related to disease severity.

Role of Skin Tests in the Diagnosis of Immediate Hypersensitivity Reactions to Taxanes: Results of a Multicenter Study.

BACKGROUND: Immediate hypersensitivity reactions (HSRs) to taxanes have been increasing in recent years, but the importance of skin tests in allergological workup has not been established. OBJECTIVE: In our study we tried to evaluate the role of prick and intradermal tests in the diagnosis of HSRs to paclitaxel and docetaxel. METHODS: In this multicenter prospective study, we enrolled patients with immediate HSRs to the aforesaid agents. Skin tests were performed on these subjects and if results were negative, intradermal tests with the culprit drug were conducted. Patients with grade 1 reactions subsequently underwent graded challenge; in cases of grade 2 or 3 reactions and/or positive test results, the culprit drug was administered with a desensitization schedule. Skin tests were also performed in 30 control subjects exposed to the taxanes without HSRs. RESULTS: A total of 84 patients (63 with HSRs to paclitaxel and 21 to docetaxel) were recruited in the period July 2015 to July 2017 by 8 centers; 58 patients (69%) developed grade 2 or 3 reactions. Prick test results were negative in all the cases, whereas intradermal test results were positive in 14 patients (10 with paclitaxel [15.9%] and 4 with docetaxel [19%]). The positivity of skin tests significantly correlated with grade 3 reactions and cutaneous involvement during HSRs. Graded challenge was performed in 16 patients without problems and 58 subjects underwent desensitization, which was well tolerated in all but 2 cases. In the control group, skin test results were negative in all the patients. CONCLUSIONS: Skin tests for taxanes seem useful and can be performed in the allergological workup of subjects with HSRs to these agents, especially in cases of severe reactions with cutaneous involvement.

Evaluation of the Potential Risk Factors for Drug-Induced Anaphylaxis in Adult Patients.

AIM: To investigate the potential risk factors in patients who have experienced anaphylaxis from drugs. METHOD: The study included 281 adult patients (median age 40 years; 76.5% female) who experienced immediate types of hypersensitivity reaction to a drug. The patients were divided into an anaphylaxis group and a nonanaphylaxis group. The anaphylaxis group was diagnosed according to the criteria of the World Allergy Organization. Skin testing with culprit drugs was performed. In the nonanaphylaxis group, drug provocation tests were performed with culprit drugs, including aspirin or diclofenac, to determine nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity. Atopy was determined by skin prick tests with the common inhalant allergens. Patients' demographics, clinical features, and baseline tryptase and total IgE levels were compared between the 2 groups. RESULTS: The median interval between the last reaction in the patient's history and the study evaluation was 7 months (range 1-120 months). In 52.3% of the patients, reactions were defined as anaphylaxis. The most common culprit drugs were NSAIDs (56.9%) and ß-lactams (34.7%). The culprit drugs were used parenterally in 13.2% of the patients. 34.9% of the patients had comorbid diseases and 24.6% used additional drugs, the most common being antihypertensives (10%). Atopy was determined in 28.8% and 28.1% of the patients were smokers. The median serum level of baseline tryptase and total IgE was 3.5 µg/L and 77 kU/L, respectively. In 46.3% of the patients, skin tests with culprit drugs were positive and the positivity ratio was higher in the anaphylaxis group (p = 0.002). Anapyhlaxis was more common in patients who were: hypertensive, atopic, using angio-tensin-converting enzyme inhibitors/angiotensin receptor blockers, and received the culprit drug parenterally (p = 0.034, p = 0.04, p = 0.03, p = 0.035, p = 0.013, and p < 0.001). In the multivariate analysis, it was observed that the parenteral usage of the drug and the presence of atopy were significantly higher in the anaphylaxis group (p < 0.001, odds ratio [OR] = 20.05, confidence interval [CI] 4.75-88.64; p = 0.012, OR = 2.1, CI 1.17-3.74). Age, smoking, family history, and serum levels of baseline tryptase and total IgE did not differ between groups. CONCLUSION: The parenteral route and atopy increase the risk of drug-induced anaphylaxis. IgE-mediated sensitivity to the culprit drug seems to facilitate anaphylaxis.

Endocan: A Novel Marker of Endothelial Dysfunction in C1-Inhibitor-Deficient Hereditary Angioedema.

BACKGROUND: Hereditary angioedema (HAE) related to C1-inhibitor deficiency is a rare autosomal dominant disorder. Vascular cell adhesion molecules (VCAM) are known as endothelial activation markers. Endocan (also called ESM-1) is proposed as an endothelial dysfunction indicator. We aimed to investigate endothelial activation in attack-free periods in HAE patients by measuring their levels of endocan and VCAM-1. METHODS: Twenty-six HAE patients (22 female, mean age 40 ± 13 years) and 38 healthy control patients (13 female, mean age 36.9 ± 12 years) were included in the study. Peripheral blood samples were collected from HAE patients during symptom-free periods and control subjects. Endocan and VCAM-1 levels were measured using the enzyme-linked immunosorbent assay method. RESULTS: The median serum levels of endocan (647 ± 101 ng/mL) and VCAM-1 (500 ± 79 ng/mL) in the HAE patients were significantly higher than in the control patients (391 ± 41 and 325 ± 4; p < 0.001 for both). CONCLUSION: The increased endocan and VCAM-1 levels may reflect an endothelial activation even in attack-free periods in HAE patients.

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.

A practical and successful desensitization protocol for immediate hypersensitivity reactions to iron salts.

Orally administered iron salts (OAS) are widely used in the management of iron deficiency anemia and hypersensitivity reactions to OAS are not common. If an offending drug is the sole option or is significantly more effective than its alternatives, it can be readministered by desensitization. The oral desensitization protocols for iron published so far concern either desensitization that was completed only over a long period or did not attain the recommended therapeutic dose. We aimed to develop a more effective protocol. We report here on 2 patients who experienced hypersensitivity reactions to OAS. After confirming the diagnosis, both patients were desensitized to oral ferrous (II) glycine sulfate complex according to a 2-day desensitization protocol. A commercial suspension of oral ferrous glycine sulfate, which contains 4 mg of elemental iron in 1 ml, was preferred. We started with a dose as low as 0.1 ml from a 1/100 dilution (0.004 mg elemental iron) of the original suspension and reached the maximum effective dose in 2 days. Both patients were successfully desensitized and they went on to complete the 6-month iron treatment without any adverse effects. Although hypersensitvity reactions to iron are not common, there is no alternative for iron administration. Therefore, desensitization has to be the choice. This easy desensitization protocol seems to be a promising option.

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-1ß, 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.

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 decreased CD4+CD25+ FoxP3+ T cells in nonstimulated allergic rhinitis patients sensitized to house dust mites.

OBJECTIVE: Regulatory (CD4(+)CD25(+)) T cells have been shown to play an important role in the development of allergic diseases. This study aims to investigate CD4(+)CD25(+) T cells, Forkhead box P3 (FoxP3(+) cells), and T-helper 1/T-helper 2 (Th1/Th2) cytokines in newly diagnosed allergic rhinitis (AR) patients. METHODS: Altogether, 10 subjects with AR and 12 age-matched nonallergic healthy subjects were included in this study. CD4(+)CD25(+) T cells, FoxP3(+) T cells in peripheral blood mononuclear cells (PBMCs) were evaluated by flow cytometry, and the Th1/Th2 cytokine levels were determined by cytometric bead array immunoassay in both PBMC supernatants and nasal lavage fluids. RESULTS: The percentage of CD4(+)CD25(+) T cells were significantly higher, whereas the percentage of FoxP3(+) cells were lower in AR patients compared with healthy subjects. In PBMC culture supernatants, interleukin-10 (IL-10) levels were significantly lower (p = .012), whereas IL-4, IL-5, and tumor necrosis factor-α (TNF-α) levels in nasal lavage fluids were higher in AR patients compared with healthy subjects (p = .026, p = .015, p = .03, respectively). CONCLUSIONS: Our findings indicate that decrease in CD4(+)CD25(+)FoxP3(+) T cell fraction and diminished levels of IL-10 are noteworthy without allergen stimulation in house dust mite AR patients.

Enhanced nerve growth factor expression by mast cells does not differ significantly between idiopathic and allergic rhinitis.

BACKGROUND: The role of neurotrophins in allergic rhinitis (AR) has been well studied, but it has not been evaluated in idiopathic rhinitis (IR). OBJECTIVE: We aimed to evaluate the nasal ß-nerve growth factor (ß-NGF) expressions of mast cells in patients with AR and IR. METHODS: Seventeen patients with house dust mites-induced persistent moderate/severe allergic rhinitis (mean age: 29.7 ± 11.96), 14 patients with idiopathic rhinitis (mean age, 29.3 ± 10.62), and 16 healthy controls (29.9 ± 11.57) were included in the study. Nasal biopsy specimens were taken from the posterior part of the inferior turbinate from all of the study subjects. Nasal ß-nerve growth factor and its receptors, pan-neurotrophin receptor p75, and tyrosine kinase A (trkA) were assessed with an immunofluorescence assay. Mast cells were determined by both an immunofluorescence assay and immunohistochemistry as tryptase-positive cells. RESULTS: The ß-NGF, trkA, and p75 receptor counts were significantly higher in AR and IR patients than in the control group (P < .001, for each), but they were not different between AR and IR patients. Similarly, the ratio of ß-NGF+ mast cells/total mast cells and the ratio of ß-NGF+ mast cells/total ß-NGF+ cells in AR and IR patients was found to be elevated when compared with the control group (P < .001, P < .001, P < .001, and P = .046, respectively); furthermore, the 2 ratios were not statistically different between the 2 patient groups. CONCLUSION: The increase in ß-NGF-expressing mast cells does not differ between idiopathic and allergic rhinitis. Therefore, we propose that mast cells do play a role in the pathogenesis of IR as important as in that of AR.

The relationship between transforming growth factor-beta1, vascular endothelial growth factor, nitric oxide and Hashimoto's thyroiditis.

BACKGROUND: Hashimoto's thyroiditis (HT) is one of the autoimmune disorders of the thyroid gland. The pathogenesis of HT has not been clearly understood. This study was designed to investigate plasma transforming growth factor-beta1 (TGF-beta1), vascular endothelial growth factor (VEGF), and nitrate/nitrite (NOx - two end products of nitric oxide [NO] metabolism) in HT. METHODS: Forty patients diagnosed HT and 40 age- and sex-matched healthy controls were included in the study. TGF-beta1 and VEGF levels were measured by ELISA, NOx levels were measured spectrophotometrically. RESULTS: Plasma TGF-beta1 and VEGF were decreased, and NOx increased in HT patients in comparison with controls. There was a significant correlation between TGF-beta1 and VEGF, and weak but significant correlation between TGF-beta1 and NOx in HT. CONCLUSION: This study indicates that TGF-beta1, VEGF and NO probably have a role in the pathogenesis of Hashimoto's thyroiditis, and development of autoimmunity. Clearly, further studies are necessary to establish the exact mechanism of TGF-beta1, VEGF and NO interaction in Hashimoto's thyroiditis.