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.

Impact of COVID-19 pandemic on the course of refractory chronic spontaneous urticaria under omalizumab treatment

Abstract Background: The course of chronic spontaneous urticaria (CSU) can be influenced by infections, depression, and stress. Objectives: Our aim was to investigate the impact of the COVID-19 pandemic on the course of refractory CSU together with patient adherence to omalizumab and treatment adjustments. Methods: Urticaria Activity Score (UAS7) was used to assess disease activity. Fear of COVID-19 Scale (FC-19s), and Depression Anxiety Stress Scale (DASS-21s) were performed to assess mental health status. All scales were performed during the Quarantine Period (QP) and Return to the Normal Period (RTNP). UAS7 Before Pandemic (BP) was recorded from the patients medical records. Results: The authors evaluated 104 omalizumab-receiving CSU patients. UAS7 scores during QP were significantly higher than those in RTNP and BP (p < 0.01). DASS-21 and FC-19 scores were significantly higher during QP compared to RTNP (p < 0.01). Nineteen (18.2%) patients ceased omalizumab, 9 patients prolonged the intervals between subsequent doses during the pandemic. UAS7 scores in QP were significantly higher in patients who ceased omalizumab than in those who continued (p < 0.001). Among patients who continued omalizumab, 22.4% had an increase in urticaria activity and higher FC-19 scores in comparison with those with stable disease activity (p = 0.008). Study limitations: The small sample size of patients with prolonged intervals of omalizumab and the lack of mental health evaluation with the same tools prior to the study. Conclusions: Fear induced by COVID-19 can determine an increase in disease activity. Therefore, patients on omalizumab should continue their treatment and prolonged interval without omalizumab can be considered in patients with good urticaria control.

Impact of COVID-19 pandemic on the course of refractory chronic spontaneous urticaria under omalizumab treatment.

BACKGROUND: The course of chronic spontaneous urticaria (CSU) can be influenced by infections, depression, and stress. OBJECTIVE: Our aim was to investigate the impact of the COVID-19 pandemic on the course of refractory CSU together with patient adherence to omalizumab and treatment adjustments. METHODS: Urticaria Activity Score (UAS7) was used to assess disease activity. Fear of COVID-19 Scale (FC-19s), and Depression Anxiety Stress Scale (DASS-21s) were performed to assess mental health status. All scales were performed during the Quarantine Period (QP) and Return to the Normal Period (RTNP). UAS7 Before Pandemic (BP) was recorded from the patients medical records. RESULTS: The authors evaluated 104 omalizumab-receiving CSU patients. UAS7 scores during QP were significantly higher than those in RTNP and BP (p < 0.01). DASS-21 and FC-19 scores were significantly higher during QP compared to RTNP (p < 0.01). Nineteen (18.2%) patients ceased omalizumab, 9 patients prolonged the intervals between subsequent doses during the pandemic. UAS7 scores in QP were significantly higher in patients who ceased omalizumab than in those who continued (p < 0.001). Among patients who continued omalizumab, 22.4% had an increase in urticaria activity and higher FC-19 scores in comparison with those with stable disease activity (p = 0.008). STUDY LIMITATIONS: The small sample size of patients with prolonged intervals of omalizumab and the lack of mental health evaluation with the same tools prior to the study. CONCLUSION: Fear induced by COVID-19 can determine an increase in disease activity. Therefore, patients on omalizumab should continue their treatment and prolonged interval without omalizumab can be considered in patients with good urticaria control.

Predictive factors of recurrence after omalizumab cessation in the elderly with urticaria: A real-life study.

Background: There are no well-defined data that help predict the recurrence risk of urticaria after omalizumab cessation in elderly patients with chronic spontaneous urticaria (CSU). Objective: We aimed to evaluate the effectiveness and safety of omalizumab and to determine the possible predictive factors for recurrence after omalizumab cessation in the elderly with CSU. Methods: A total of 193 patients with CSU treated with omalizumab were included and divided into two groups according to age: group 1, ages 18-64 years (n = 127), and group 2, ages ≥ 65 years (n = 66). Demographics, clinical features, immunoglobulin G (IgG) anti-thyroid peroxidase antibody (anti-TPO), serum total IgE were analyzed. The IgG anti-TPO/total IgE ratio was calculated. Pretreatment 7-day urticaria activity scores, medication scores, and urticaria control test results were compared with those after treatment periods. Adverse effects were also evaluated. Results: The most common adverse effect of omalizumab treatment was injection-site reactions (4.7%) in both groups. Omalizumab was ceased after 24 weeks in 40.9% and in 73.1% in group 1 and group 2, respectively (p < 0.001). CSU recurred after omalizumab discontinuation in 9 and 15 patients in group 1 and in group 2, respectively (p < 0.001). The median baseline IgG anti-TPO was higher in patients with recurrent CSU in group 2 than in those in group 1 (p = 0.002). In group 2, the cutoff values of IgG anti-TPO and the IgG anti-TPO/total IgE ratio were 54.83 IU/mL and 0.45 for recurrence, respectively. Conclusion: Omalizumab is effective and safe in elderly patients with CSU. The serum baseline IgG anti-TPO level and the IgG anti-TPO/total IgE ratio could serve as predictors of recurrence in CSU after omalizumab cessation in elderly patients.

Clinical effects of intranasal corticosteroids on nasal symptoms in subjects with chronic rhinitis during COVID-19.

Background: The clinical effects of intranasal corticosteroids (INC) on nasal symptoms and the clinical course of coronavirus disease 2019 (COVID-19) in subjects with chronic rhinitis (CR) seem unclear. Objective: To evaluate the clinical effects of INCs on nasal symptoms in subjects with CR and with COVID-19. Methods: In subjects with CR and diagnosed with COVID-19 at four tertiary centers, quality of life and nasal symptoms were assessed by using the 22-item Sino-Nasal Outcome Test (SNOT-22) and the visual analog scale (VAS), respectively. In subjects with allergic rhinitis, nasal symptoms were also assessed on the total symptom score-6 (TSS-6) scale. The subjects were then allocated into two groups according to whether or not they used INCs while infected with the severe acute respiratory syndrome coronavirus 2 (group 1 and group 2, respectively). The subjects in group 2 were divided into two subgroups according to the use of antihistamines and/or leukotriene receptor antagonist or not (group 2a and group 2b, respectively). All the scores were compared before and during COVID-19 among the three groups. Results: A total of 71 subjects (21 in group 1, 24 in group 2a, and 26 in group 2b) were enrolled. The total scores of the SNOT-22 increased remarkably in all the groups during the infection when compared with the pre-COVID-19 scores (p < 0.001 in each group). However, the difference between the pre-COVID-19 and COVID-19 values revealed a lower decrease in the senses of smell and/or taste in group 1 than in group 2a and group 2b (p = 0.015, adjusted p = 0.045; and p = 0.001, adjusted p = 0.002, respectively). There were no significant differences in other COVID-19 findings, VAS, and TSS-6 scores among the groups (all p > 0.05). Conclusion: INCs in subjects with CR seemed protective against the decrease in smell and/or taste observed during COVID-19 and do not aggravate the clinical course of COVID-19.

Adherence to subcutaneous immunotherapy with aeroallergens in real-life practice during the COVID-19 pandemic.

BACKGROUND: The success of subcutaneous immunotherapy (SCIT) mostly depends on regular injections. Our aim was to investigate adherence to SCIT with aeroallergens during the COVID-19 pandemic and demonstrate clinical consequences of treatment disruptions in real life. METHODS: Visual analogue scale for quality of life (VAS-QoL), VAS for symptom scores (VAS-symptom), medication scores (MSs), and total symptom scores (TSS-6) were recorded during the pandemic in 327 adult allergic rhinitis and/or asthmatic patients receiving maintenance SCIT, and these scores were compared with the pre-pandemic data. Patients were grouped according to SCIT administration intervals; no delay (Group 1), <2 months (Group 2), and ≥2-month intervals (Group 3). RESULTS: A total of 104 (31.8%) patients (Group 3) were considered as nonadherent which was mostly related to receiving SCIT with HDMs and using public transportation for reaching the hospital. Median MS, VAS-symptom, and TSS-6 scores of Group 3 patients during the pandemic were higher than the pre-pandemic scores (p = 0.005, p < 0.001, p < 0.001, respectively), whereas median VAS-QoL scores of Group 3 during the pandemic were lower than the pre-pandemic scores (p < 0.001). Median TSS-6 and VAS-symptom scores were the highest in Group 3 compared with other groups (p < 0.001 for each comparison). Median VAS-QoL scores were the lowest in Group 3 compared with Group 1 and Group 2 (p < 0.001, p = 0.043, respectively). CONCLUSION: When precautions in allergy clinics are carefully applied, adherence to SCIT can be high during a pandemic. Patients must be encouraged to regularly adhere to SCIT injections since delays in SCIT administration can deteriorate clinical symptoms.

Evaluation of skin test indications for general anesthetics in real life: a prospective cohort study.

BACKGROUND: In daily practice, atopic patients and those who have other drug allergies are referred to allergy clinics for evaluation of possible general anesthetic allergy despite the fact that it is not recommended in recent guidelines. OBJECTIVE: The aim of this prospective study is to determine the negative predictive value of skin tests for common general anesthetic drugs prior to general anesthesia in atopic patients and in patients who had drug allergies by including the data of those who had previously tolerated or reacted to general anesthesia. METHODS: A database program was constituted to collect the preoperative skin test data of patients referred to our clinic between 2013 and 2018. Demographic and clinical history, medications implemented during perioperative period, reactions, and results of skin tests performed with anesthetic drugs and latex were evaluated. RESULTS: Four hundred fifty-nine out of the total 1167 patients referred fulfilled the inclusion criteria for further evaluation. Nearly 75% of the patients were female and mean age was 46.3 ±â€¯14.3 years. History of hypersensitivity reactions (HRs) due to NSAIDs and/or antibiotics, radiocontrast agents, local anesthetics, and food were present in the 53.1%, 4.1%, 1.5%, and 2.0%, respectively. The negative predictive values of skin tests for general anesthetics were in the range of 80-100%. Only 4 patients (0,87%) experienced HRs during operation. CONCLUSION: These real-life data reveal high rates of negative predictive value of skin tests with general anesthetic drugs and a low reaction rate in atopic patients and in patients with allergy to other drugs.

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.

Impact of anxiety, stress and depression related to COVID-19 pandemic on the course of hereditary angioedema with C1-inhibitor deficiency.

BACKGROUND: Hereditary angioedema (HAE) attacks can be provoked with psychological factors. The aim of this study was to assess the effects of anxiety, depression and stress related to COVID-19 pandemic on disease activity of HAE patients during the quarantine period (QP) and the return to normal period (RTNP). METHODS: This study was conducted between March 2020 and September 2020 in four allergy centres. Demographic, clinical features and mental health status were evaluated in QP (from March to the beginning of June) and RTNP (from June to the beginning of September) applied by the government. The 10-point visual analogue scale (VAS10) was used to define the severity of HAE attacks. Depression, Anxiety and Stress Scales-21 (DASS-21) and Fear of COVID-19 (FC-19) scale were performed to assess mental health status. RESULTS: 139 HAE patients were included in the study. In QP, median attack numbers and median VAS10 scores were 5 (min-max: 0-45) and 6 (min-max: 0-10), respectively. HAE attack numbers, DASS-21 stress, anxiety, depression and total DASS-21 scores, and FC-19 scores were higher in QP than RTNP (p = 0.001, p < 0.001, p = 0.001, p < 0.001, p < 0.001, p < 0.001, respectively). However, there was no difference in attack severity scores between the two periods (p > 0.05). CONCLUSIONS: This study revealed that the restriction measures during COVID-19 outbreak cause an increase in the number of HAE attacks in relation to anxiety, depression, stress and fear of COVID-19 pandemic. Therefore, it is important to provide psychological support to HAE patients during the pandemic.

Interleukin-10 is increased in successful drug desensitization regardless of the hypersensitivity reaction type.

BACKGROUND: Little is known about the mechanism of desensitization in hypersensitivity drug reactions. OBJECTIVE: The aim of this study was to evaluate the effects of drug desensitization on some cytokine levels in patients desensitized for drug hypersensitivity reactions. METHODS: Patients with a hypersensitivity reaction to any drug for whom desensitization was planned with the culprit drug, patients who could tolerate the same drugs and healthy subjects who were not exposed to these drugs were enrolled. Bead-based Milliplex MAP multiplex technology was used to determine interleukin (IL)-4, IL-5, interferon-γ and IL-10 levels in the sera of the subjects as a baseline and 24 hours after desensitization had been completed in the patients. RESULTS: A total of 26 patients (16 female [61.5%]; mean age 48.46 ± 15.97 years old), 10 control patients (5 female [50%]; mean age 47.4 ± 15.4 years old) and 5 healthy subjects (3 female [60%]; mean age 34.2 ± 5.6 years old) were enrolled. Four of the 26 patients did not tolerate the procedure and were grouped as the 'unsuccessful desensitization group' whereas 22 patients successfully completed the procedure and formed the 'successful desensitization group.' Baseline cytokine levels in the 3 groups were not statistically different. Postdesensitization IL-10 levels in the successful desensitization group were significantly higher than their initial levels (p = 0.005) whereas none of the cytokine levels significantly changed in the unsuccessful desensitization group. The rise in IL-10 levels was greater in chemotherapeutic desensitizations when compared to other drugs (p = 0.006). CONCLUSION: Successful desensitization independent of the hypersensitivity reaction type seems to be related to the increase of IL-10.

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.

Evaluation of the left venticular systolic function with the measurement of global longitudinal strain by Speckle tracking echocardiography in anaphylaxis.

BACKGROUND: It is not known how cardiac functions are affected during anaphylaxis. OBJECTIVE: Our aim was to measure the cardiac functions shortly after an anaphylaxis attack using a new technique that detects subclinical left ventricular dysfunction. METHODS: Patients in our hospital who experienced anaphylaxis and urticaria (control group) due to any cause were included in the study. Tryptase levels were measured on the third hour of the reaction and 6 weeks later. Left ventricular systolic functions were evaluated with global strain measurement using echocardiography, approximately 4 hours and 6-week post reaction. RESULTS: Twelve patients were included in the anaphylaxis group (83.3% female; mean age, 43.25 ± 9.9 years). The causes of anaphylaxis were drug ingestion (n = 11) and venom immunotherapy. Eight of the anaphylactic reactions (66.7%) were severe and in 9 reactions (75%) tryptase levels increased. In the anaphylaxis group, strain values measured shortly after anaphylaxis were significantly lower than those calculated 6 weeks later (p < 0.001) and tryptase levels significantly increased (p = 0.002). The strain values measured both shortly after anaphylaxis and 6 weeks later did not differ according to severity of anaphylaxis. In severe anaphylaxis, tryptase levels during anaphylaxis and 6 weeks later were significantly higher (p = 0.019, p = 0.035). The control group evidenced no differences regarding strain and tryptase levels measured at reaction and 6 weeks later. At reaction, in the anaphylaxis group, the tryptase levels were higher and the strain values were lower than those in the urticaria group (p = 0.007, p = 0.003). CONCLUSION: Cardiac dysfunction may develop during an anaphylaxis independent of severity of reaction.

An unusual dual hypersensitivity reaction to moxifloxacin in a patient.

Both immediate and nonimmediate type hypersensitivity reactions (HRs) with a single dose of quinolone in the same patient have not been previously reported. A 47-year-old female patient referred to us because of the history of a nonimmediate type HR to radio contrast agent and immediate type HR to clarithromycin. She experienced anaphylaxis in minutes after the second dose of 50 mg when she was provocated with moxifloxacin. She was treated immediately with epinephrine, fluid replacement and methylprednisole and pheniramine. On the following day she came with macular eruptions, and she was treated with methylprednisolone. The positive patch test performed with moxifloxacin as well as the lymphocyte transformation test proved the T-cell mediated HR. In order to prove the immediate type HR, basophil activation test was performed but was found negative. This case report presents for the first time the 2 different types of HRs in a patient with a test dose of quinolone.

Generalized Fixed Drug Eruption Induced by Fluconazole Without Cross-Reactivity to Itraconazole: Lymphocyte Transformation Test Confirms the Diagnosis.

We present a rare case of generalized fixed drug eruption caused by fluconazole. A 45-year-old female patient was referred to our outpatient clinic because of suspicious drug eruptions that occurred 5 months earlier and resolved within a month. The patient had sequela of hyperpigmentation on her arms, legs, back, and abdomen after oral administration of the fourth dose of 150 mg of fluconazole once daily because of vaginal candidiasis. Patch tests with the culprit drug applied both on unaffected skin areas and over one of the lesions were negative. A lymphocyte transformation test was performed and in response to fluconazole, CD4+ T cells significantly proliferated. Because the patient needed a safe antifungal drug for her recurrent vaginal candidiasis symptoms, a single-blind placebo-controlled drug provocation test was performed with itraconazole and was negative. Accordingly, 200 mg of itraconazole once daily was given for 10 days safely.

Diagnostic Value of Oral Challenge Testing in the Diagnosis of Macrolide Hypersensitivity.

BACKGROUND: Hypersensitivity reactions (HRs) to macrolides are rare. OBJECTIVE: The aim of this study was to evaluate the diagnostic value of in vivo tests in the diagnosis of HRs to macrolides and also to assess cross-reactivity between 4 different macrolides (clarithromycin, dirithromycin, spiramycin, and azithromycin) belonging to 3 different groups. METHODS: Twenty-five patients with a history of immediate or delayed-type HRs to at least 1 macrolide and 20 healthy control subjects underwent skin testing for both the culprit and alternative macrolides. Then, all subjects underwent single-blind drug provocation tests (SBDPTs) with these drugs. RESULTS: Twenty-one patients (84%) described an early reaction, whereas the remaining 4 (16%) had delayed-type reactions. Skin prick test results with culprit macrolides were positive in only 2 patients who had experienced anaphylaxis. These 2 and another 4 patients with anaphylaxis history and 6 patients with negative skin test results who did not give consent were not challenged. A total of 13 patients with negative skin test results were challenged with the culprit drugs and all of them experienced HRs during the SBDPTs. Skin test results with alternative drugs were positive in only 2 patients with negative SBDPT results. Conversely, 5 patients with negative skin test results reacted to SBDPTs with alternative macrolides. In healthy control subjects, the skin test results were positive in 3 patients (1 positivity with clarithromycin, 2 positivity with spiramycin) whereas all DPT results were negative. CONCLUSIONS: Our results suggested that DPT is the only reliable method to predict macrolide hypersensitivity as well as to detect cross-reactivity between macrolides.

High adherence to subcutaneous immunotherapy in a real-life study from a large tertiary medical center.

BACKGROUND: Studies on real-life adherence to subcutaneous allergen immunotherapy (SCIT) for respiratory allergy are scarce. The aim of this study was to evaluate adherence to SCIT. METHODS: The patients prescribed SCIT for allergic rhinitis and/or asthma in 2009-2011 were contacted in 2014 and asked whether they completed at least the 3 years of SCIT and/or whether they suspended the treatment for at least 2 months. The Total Symptom Score-6, visual analog scale (VAS), asthma control test (ACT), medication scores, quality of life (QoL) scores, and immunotherapy satisfaction scores with VAS obtained before the initiation of SCIT in the first year and at the end of SCIT were compared. RESULTS: A total of 204 patients (136 female [66.7%]; mean age, 38.83 ± 12.02 years) were included; 73% (149/204) were both compliant and persistent; 14% (29/204) were only persistent; and, overall, 87.3% (178/204) were considered adherent. Adherence was more frequent in female patients (95% CI, 62.3-76.3%; p = 0.018). Medication, symptom, ACT, and QoL scores in the first year and at the end of the treatment were significantly lower than the initial scores, and the immunotherapy satisfaction scores at the end of treatment were higher than the scores in the first year in the patients who were adherent (p < 0.001 for each score). CONCLUSION: The adherence rate to SCIT in our study was relatively high, in contrast to previous real-life data. Results of our study indicated that a close relationship between allergists and their patients during SCIT and the follow-up period in the same center improved the outcome of SCIT.

Usefulness of In Vivo and In Vitro Diagnostic Tests in the Diagnosis of Hypersensitivity Reactions to Quinolones and in the Evaluation of Cross-Reactivity: A Comprehensive Study Including the Latest Quinolone Gemifloxacin.

PURPOSE: Reports evaluating diagnosis and cross reactivity of quinolone hypersensitivity have revealed contradictory results. Furthermore, there are no reports investigating the cross-reactivity between gemifloxacin (GFX) and the others. We aimed to detect the usefulness of diagnostic tests of hypersensitivity reactions to quinolones and to evaluate the cross reactivity between different quinolones including the latest quinolone GFX. METHODS: We studied 54 patients (mean age 42.31±10.39 years; 47 female) with 57 hypersensitivity reactions due to different quinolones and 10 nonatopic quinolone tolerable control subjects. A detailed clinical history, skin test (ST), and single-blind placebo-controlled drug provocation test (SBPCDPT), as well as basophil activation test (BAT) and lymphocyte transformation test (LTT) were performed with the culprit and alternative quinolones including ciprofloxacin (CFX), moxifloxacin (MFX), levofloxacin (LFX), ofloxacin (OFX), and GFX. RESULTS: The majority (75.9%) of the patients reported immediate type reactions to various quinolones. The most common culprit drug was CFX (52.6%) and the most common reaction type was urticaria (26.3%). A quarter of the patients (24.1%) reacted to SBPCDPTs, although their STs were negative; while false ST positivity was 3.5% and ST/SBPCDPTs concordance was only 1.8%. Both BAT and LTT were not found useful in quinolone hypersensitivity. Cross-reactivity was primarily observed between LFX and OFX (50.0%), whereas it was the least between MFX and the others, and in GFX hypersensitive patients the degree of cross-reactivity to the other quinolones was 16.7%. CONCLUSIONS: These results suggest that STs, BAT, and LTT are not supportive in the diagnosis of a hypersensitivity reaction to quinolone as well as in the prediction of cross-reactivity. Drug provocation tests (DPTs) are necessary to identify both culprit and alternative quinolones.

Impact of high serum Immunoglobulin E levels on the risk of atherosclerosis in humans.

BACKGROUND: Epidemiological studies show that immunoglobulin E (IgE) levels were higher in subjects with acute coronary events. However, it is unknown if the increased IgE level is a marker of future coronary incidents and whether it may be regarded as a risk factor of an ischemic heart disease. OBJECTIVE: Our aim was to investigate the relationship between IgE levels and some atherosclerotic markers in patients without known atherosclerotic disease. METHODS: Fifty patients (mean age, 40.96 ± 10.8 years) with high serum IgE levels due to various conditions who did not display evidence of an atherosclerotic disease and 30 healthy control subjects (mean age, 47 ± 8.27 years) were included in the study. Atherosclerotic disease markers including adhesion molecules like vascular cell adhesion molecule-1, intercellular adhesion molecule-1, proinflammatory cytokines such as interleukin-6, endothelin-1, and systemic inflammatory markers such as high sensitivity C-reactive protein were determined by enzyme-linked immunosorbent assay (ELISA). Endothelial functions of the coronary arteries were determined by coronary flow reserve (CFR) measurements and carotid intima media thickness using transthoracic Doppler echocardiography. RESULTS: CFR was significantly lower in the patient group when compared with the control group (p<0.001; 95% confidence interval, -0.79 to-0.20) while carotid media thicknesses were not different between 2 groups. There were no differences in ELISA test results between the 2 groups. CONCLUSION: Our results showed that CFR as an early marker of endothelial dysfunction was significantly lower in patients with high IgE levels. This finding seems to support the role of IgE in the vascular pathology of atherosclerosis.

[A case of rib tuberculosis and chest wall abscess with multi-drug hypersensitivity reactions]. / Çok ilaca asiri duyarlilik reaksiyonu görülen bir kot tüberkülozu ve gögüs duvari apsesi olgusu.

Extrapulmonary tuberculosis is the reactivation of the remaining latent organism which spreads during primary infection by the lymphohematogenous way. It should be considered in the differential diagnosis especially in endemic countries for tuberculosis. Tuberculosis (TB) treatment is based on the principle of the combined use of several drugs. As a result of the combination therapy there can be life threatening side effects which can lead to improper use of medications and may also cause drug resistance. In this report, we present an 85-year-old male patient desensitized due to the development of allergy against multi-drugs with rib tuberculosis and chest wall abscess to whom, culture, drug susceptibility and genotypical tests were applied. In November 2012, the patient applied to a medical center with complaints of swelling and pain under the right rib, underwent rib resection and eventually diagnosed as rib TB by histopathological examination. However, the anti-TB treatment was discontinued due to the hypersensitivity reactions in the skin and in addition to the hepatic and renal dysfunction side effects. The patient had widespread redness, rash and pruritus on the body and the laboratory findings were as follows; ALT: 114 U/L, AST: 152 U/L, ALP: 93 U/L, GGT: 26U/L, blood urea nitrogen (BUN): 26 mg/dL and creatinine: 1.7 mg/dL. After the disapperance of the complaints within 3 days of drug discontinuation, isoniazid treatment was initiated. However, the new treatment was also discontinued when the reactions reoccurred. Afterwards, the patient developed hypersensitivity reactions against the combination of streptomycin and ethambutol. The patient refused any further treatment and was discharged from the hospital. The patient was untreated for the last 5 months and admitted to our clinic with a fistulized swelling and abscess in the right chest wall. Bacteria was not detected in the acid-fast staining of the abscess material, however Mycobacterium tuberculosis was isolated from culture by MGIT (Mycobacteria Growth Incubator Tube; BBL MGIT, BD, USA) system. The spoligotyping revealed that the genotype was Haarlem 1. Major drug susceptibility testing against rifampin, streptomycin, ethambutol, isoniazid, and pyrazinamide yielded sensitivity to those drugs. Minor drug susceptibility testing against paraaminosalicylic acid, ethionamide, kanamycin, capreomycin and ofloxacin was found to be sensitive. A regimen of isoniazid 300 mg/day, ethambutol 1000 mg/day and moxifloxacin 400 mg/day was initiated. Rapid oral desensitization against isoniazid and ethambutol were repeated on two consecutive days. The patient continued antituberculosis therapy for 12 months without adverse reactions. The chest wall fistula was closed. Abscess was drained surgically. Clinical and radiological improvements were achieved. The patient remains clinically disease free and continues his regular follow ups. This case is presented to emphasize about the importance of culture and susceptibility testing in extrapulmonary tuberculosis cases and desensitization in drug hypersensitivity reactions.