Delayed drug hypersensitivity to anti-tuberculosis drug: a new desensitization scheme.

Introduction: Tuberculosis is a communicable illness and one of the leading causes of death, especially in developing countries like Turkey. One of the problems that must be managed well in the treatment of tuberculosis is drug hypersensitivity. The first-line agents are very important for the success of treatment. Alternative drugs are more toxic and less successful in treatment. Therefore, it is very important to be able to include first-line drugs in the post-hypersensitivity regimen. At this point, the success of desensitization comes to the fore. There are fewer studies on rapid drug desensitization in delayed-type drug hypersensitivity to anti-tuberculosis drugs. Aim: The primary aim of the study was to determine the prevalence of delayed-type hypersensitivity reactions in drug-sensitive cases; the secondary aim was to determine the appropriate treatment management. Material and methods: This was a retrospective study. Demographic features, tuberculosis diagnostic indicator, clinical signs of developing a hypersensitivity reaction, reaction time, desensitization scheme and treatment were evaluated. Results: A total of 41 tuberculosis cases were included in the study. Twenty-six of the cases were male; mean age (mean ± SD) 55.44 ±16.93 years; 70.7% of them were diagnosed bacteriologically; 70.7% of them were diagnosed with pulmonary tuberculosis. The most common skin finding was maculopapular drug eruption. The development time (mean ± SD) of the reaction in patients who developed a reaction was 34.93 ±39.62 days. The responsible agent could be identified in 15 reactions. The most common drug responsible for the reaction was rifampicin. Successful desensitization was achieved in 19 (46.3%) cases with the sensitive regimen. The duration of treatment was 8.97 ±3.44 months. When evaluated in terms of treatment results, cure and treatment completion were accepted as treatment success. In this case, 30 (73.2%) patients successfully completed the treatment. Conclusions: Our study is one of the largest series in which delayed-type hypersensitivity develops under tuberculosis treatment and the desensitization scheme is recommended. A practical, easy desensitization scheme had been shared in this paper.

Picturing asthma in Turkey: results from the Turkish adult asthma registry.

INTRODUCTION: National data on asthma characteristics and the factors associated with uncontrolled asthma seem to be necessary for every country. For this purpose, we developed the Turkish Adult Asthma Registry for patients with asthma aiming to take a snapshot of our patients, thereby assigning the unmet needs and niche areas of intervention. METHODS: Case entries were performed between March 2018 and March 2022. A web-based application was used to record data. Study outcomes were demographic features, disease characteristics, asthma control levels, and phenotypes. RESULTS: The registry included 2053 patients from 36 study centers in Turkey. Female subjects dominated the group (n = 1535, 74.8%). The majority of the patients had allergic (n = 1158, 65.3%) and eosinophilic (n = 1174, 57.2%) asthma. Six hundred nineteen (32.2%) of the patients had obese asthma. Severe asthma existed in 670 (32.6%) patients. Majority of cases were on step 3-5 treatment (n: 1525; 88.1%). Uncontrolled asthma was associated with low educational level, severe asthma attacks in the last year, low FEV1, existence of chronic rhinosinusitis and living in particular regions. CONCLUSION: The picture of this registry showed a dominancy of middle-aged obese women with moderate-to-severe asthma. We also determined particular strategic targets such as low educational level, severe asthma attacks, low FEV1, and chronic rhinosinusitis to decrease uncontrolled asthma in our country. Moreover, some regional strategies may also be needed as uncontrolled asthma is higher in certain regions. We believe that these data will guide authorities to reestablish national asthma programs to improve asthma service delivery.

Country-based report: the safety of omalizumab treatment in pregnant patients with asthma

Background/aim: We aimed to report outcomes of pregnant patients with asthma under omalizumab treatment and their infants in our country. Materials and methods: Patients with asthma who received omalizumab for at least 6 months and at least one dose during their pregnancy were retrospectively evaluated using a questionnaire regarding their disease and therapy and the health of their infants. Results: Twenty pregnant patients and their 23 infant's data were analyzed. The mean delivery age was 31.8 ± 7.4 years. They received omalizumab for 28.9 ± 21.8 months. Eight (36.4%) patients showed exacerbation of the disease during pregnancy. Forced expiratory volume in 1 s (FEV1) and asthma control test (ACT) scores at the starting time of omalizumab administration, first month of the pregnancy, and after delivery were 71 ± 18%, 83.4 ± 10.5%, and 80.5 ± 13% (FEV1), and 11.9 ± 4.9, 20.2 ± 2.6, and 20.4 ± 2.2 (ACT), respectively. One patient gave birth to twin infants, two patients to two infants each in different years, and 17 to one infant each. Three (13%) infants had low birth weight and five (21.7%) were born prematurely. No congenital anomalies were detected. Seven (30.4%) infants presented atopic diseases during their life. Conclusion: Omalizumab treatment during pregnancy seems to be safe for both patients and their infants.

Turkish version of the Drug Hypersensitivity Quality of Life Questionnaire: assessment of reliability and validity.

PURPOSE: The first disease-specific quality-of-life questionnaire in patients with drug hypersensitivity, Drug Hypersensitivity Quality of Life Questionnaire (DrHy-Q), was developed and validated recently. The aim of this study was to assess validity, reliability and responsiveness to interventions of the Turkish version of the DrHy-Q. METHODS: The Turkish version of the DrHy-Q was administered to prospectively enrolled 736 patients with drug hypersensitivity from ten allergy units. To assess validity, all patients completed the validated Turkish version of Psychological General Well-Being Index (PGWBI). For test-retest reliability, 182 patients completed the DrHy-Q 1 week after the first questionnaire administration without any intervention. Responsiveness was assessed on 97 patients who had a DrHy-Q recorded at a follow-up visit after the intervention. RESULTS: The internal consistency and test-retest reliability of the scale were adequate (Cronbach's alpha = 0.934, intra-class correlation coefficient = 0.783). The DrHy-Q scores showed weak negative correlations with the PGWBI total and domain scores (r = - 0.378 to -0.254, p < 0.001). DrHy-Q was able to discriminate the patients with one drug hypersensitivity reaction from the patients with two and above two reactions (p = 0.012 and p < 0.001, respectively), and the patients who experienced a respiratory reaction from the patients who did not (p = 0.018). However, it did not discriminate the patients with comorbid disease including psychiatric comorbidity (p > 0.05). The baseline DrHy-Q scores were significantly higher than the post-intervention scores (p = 0.008). CONCLUSION: The Turkish version of DrHy-Q is reliable and valid for evaluating quality of life in patients with drug hypersensitivity, and it appeared responsive to interventions.

Immediate-type hypersensitivity reactions due to antituberculosis drugs: a successful readministration protocol.

BACKGROUND: Little is known about drug hypersensitivity reactions from antituberculosis drugs. OBJECTIVE: To determine the frequency, risk factors, and characteristics of immediate-type hypersensitivity reactions from first-line antituberculosis drugs and to evaluate the usefulness of a readministration protocol for culprit drugs in this group of patients. METHODS: The study population consisted of patients with tuberculosis who were hospitalized and treated in the authors' hospital in 2011. Demographics and disease and treatment characteristics of patients with immediate-type hypersensitivity from antituberculosis drugs were compared with the other patients. Culprit drugs were readministered gradually according to a defined protocol to patients with immediate-type hypersensitivity. RESULTS: Tree hundred seventy-nine patients were included in the study. Eighteen immediate-type hypersensitivity reactions were detected in 13 patients (3.43%). The only identified risk factor was female sex (odds ratio 4.085). Isoniazid, rifampicin, pyrazinamide, and ethambutol were readministered in 11 patients and rifampicin was readministered in 2 patients, with 6- to 8-step protocols for each drug. Only in 2 patients did allergic reactions with rifampicin develop during the procedure. In these patients, after treatment and complete remission of allergic symptoms, the last tolerated dose was administered and the protocol was completed with the same adjustments. CONCLUSION: Immediate-type allergic reactions from antituberculosis drugs are not rare and not related to disease or treatment characteristics. The protocols used in this study provide a useful and safe method for readministration of culprit drugs to patients with antituberculosis drug hypersensitivity.

Drug hypersensitivity in drug-resistant tuberculosis.

Objective: To evaluate drug resistant tuberculosis patients who developed drug hypersensitivity to antituberculosis drug. Methods: This was a retrospective study. The primary aim of the study is to determine the demographic and clinical characteristics of patients who develop drug hypersensitivity in drug resistant tuberculosis patients. The secondary aim of the study is to examine the treatment results. Demographic features, tuberculosis diagnostic indicator, clinical signs of developing hypersensitivity reaction, reaction time, and treatment were evaluated. Results: A total of 25 patients were included in the study. The prevalence of hypersensitivity in drug resistance patients was 11.9%. Twelve (48%) of the cases were women. Mean age (mean ± SD) was 37.24 ± 14.44 years; early type hypersensitivity reaction in 13 (52%). Three patients were isoniazid resistant; 19 patients were multidrug-resistant (MDR); 2 patients were pre-extensive drug resistant (Pre-XDR), 1 patient was extensive drug resistance (XDR) tuberculosis. The most common skin findings were maculopapular eruption and urticaria. But also we had seen isole angiodema, urticaria and angioedema, erythema multiforme, lichenoid drug eruption and drug rash with eosinophilia and systemic symptoms. In patients who developed a hypersensitivity reaction, the responsible agent was identified in 14 cases in total. Among the drugs, pyrazinamide, ethambutol, moxifloxacin, amikacin, para amino salicylic, prothionamide, and cycloserine are the responsible agents. When evaluated in terms of treatment results, 15 (60%) patients successfully completed the treatment. Conclusion: Our study is the first study in the literature that evaluated the drug hypersensitivity in drug resistance tuberculosis patients. Drug hypersensitivity that develops with tuberculosis treatment may lead to discontinuation or change in treatment. It can cause treatment failure, drug resistance, relapse, and even death. In resistant tuberculosis, the already existing resistance pattern may become more difficult to treat. Success can be achieved with the right management in these patients who have few treatment options, more drug side effects, and high treatment failure rates. The established regimen should be curative and prevent recurrence.

Stepwise Approach in Asthma Revisited 2023: Expert Panel Opinion of Turkish Guideline of Asthma Diagnosis and Management Group.

Introduction of inhaled corticosteroids (ICS) has been the cornerstone of the long-term management of asthma. ICSs either alone or in combination with long-acting beta-2 agonists have been shown to be associated with favorable asthma outcomes. However, asthma control is still reported to be below expectations all around the world. Research in the last decades focusing on the use of ICS/formoterol both as maintenance and as needed (maintenance and reliever therapy approach) showed improved asthma outcomes. As a result of recent developments, Turkish Asthma Guidelines group aimed to revise asthma treatment recommendations. In general, we recommend physicians to consider the risk factors for poor asthma outcomes, patients' compliance and expectations and then to determine "a personalized treatment plan." Importantly, the use of short-acting beta-2 agonists alone as a symptom reliever in asthma patients not using regular ICS is no longer recommended. In stepwise treatment approach, we primarily recommend to use ICS-based controllers and initiate ICS as soon as possible. We define 2 different treatment tracks in stepwise approaches as maintenance and reliever therapy or fixed-dose therapy and equally recommend each track depending on the patient's risks as well as decision of physicians in a personalized manner. For both tracks, a strong recommendation was made in favor of using add-on treatments before initiating phenotype-specific treatment in step 5. A strong recommendation was also made in favor of using biologic agents and/or aspirin treatment after desensitization in severe asthma when indicated.

Treatment and management of hypersensitivity reactions developed against anti-tuberculosis drug.

Background: The World Health Organization Global Tuberculosis Report 2021 defines tuberculosis as the second infectious disease that causes sickness and death after COVID 19 and ranks it as the 13th among the global causes of death. However, the prevalence of the patients developing a hypersensitivity reaction against antituberculosis treatment is yet unknown. This study aimed to investigate the prevalence of drug allergy against antituberculosis treatment and the management of such a problem. Methods: This is a case--control study. All patients hospitalized in the tuberculosis inpatient service between February 01, 2015 and May 01, 2021 due to hypersensitivity reaction or who developed hypersensitivity during hospitalization were included in the case group. Patients who received inpatient treatment between the same dates and did not develop any drug allergy were included in the control group. The demographic characteristics of the patients, the tuberculosis diagnostic indicator, the type of hypersensitivity reaction that developed, the duration of the manifestation of the reaction and its treatment were evaluated for the purpose of the study. Results: A total of 2677 patients were hospitalized in the tuberculosis inpatient service between the specified dates. Two hundred and ten patients were consulted for drug hypersensitivity reactions in the Allergy Clinic. The prevalence of drug allergy in inpatients was calculated as 7.8%. One hundred and forty-eight patients examined by the authors were included in the study. Seventy-nine of the 148 patients (53.4%) who developed a hypersensitivity reaction were male, the mean age of these patients was 47.20 ± 18.95 years, 89.2% (n = 132) were citizens of the Republic of Turkey, 7.4% (n = 11) of the patients had received tuberculosis treatment before, 16.9% (25) had developed antituberculosis drug resistance and the bacteriological diagnosis was present in 79.7% (118) of the patients. Chi-square test results applied in the allergy group revealed that the risk of developing a hypersensitivity reaction is statistically significantly higher in female patients (P < 0.001), Turkish citizen patients (P = 0.004), in new cases (P = 0.017), in the group not diagnosed bacteriologically (histopathologically, clinically, and radiologically) (P = 0.006). The results of the logistic regression analysis performed also revealed that the risk of developing a hypersensitivity reaction is statistically significantly higher in female patients (P = 0.006), Turkish citizen patients (P = 0.023), in new cases (P = 0.017) and in the group not diagnosed bacteriologically (histopathologically, clinically, and radiologically) (P = 0.006). The success of the treatment was higher in the group that developed a hypersensitivity reaction compared to the control group. About 63.5% (94) of the patients examined developed Type I hypersensitivity reactions, whereas 36.7% (53) of the patients examined developed Type IV hypersensitivity reactions. Type I and Type IV reactions were observed simultaneously in a single patient. Considering the prevalence of developing a hypersensitivity reaction, pyrazinamide was determined as the drug inducing the hypersensitivity reaction in 25 (48.1%) patients. This figure was 15 patients (28.2%) for rifampicin, nine patients (17.3%) for isoniazid, and five patients (9.6%) for ethambutol. As a result, even patients who developed Type I or Type IV reactions were able to complete their antituberculous drug regimens with successful desensitization. Conclusion: The risk of developing an allergic reaction in patients who are administered on antituberculosis treatment is common, particularly in the first 2 months of treatment. However, we believe that the compliance of the patients to the antituberculosis treatment has been improved at the end of appropriate management of hypersensitivity reactions and the treatment results in success.

Management of type 1 immediate hypersensitivity reactions to antituberculosis drug: succesful desensitization.

OBJECTIVE: In this study, it was aimed to investigate the prevalence of type 1 hypersensitivity reaction under tuberculosis treatment and the management of hypersensitivity. METHODS: The study is a case series. All of the patients who were hospitalized between 01.02.2015-01.05.2021 were examined. All patients who developed a drug-induced type 1 immediate hypersensitivity reaction were included. Antituberculosis drugs were given with the protocol made by Buhari et al. However, unlike what is stated in the protocol, pyrazinamide was given last during the administration of the drugs. RESULTS: 2677 patients received inpatient tuberculosis treatment; type 1 immediate hypersensitivity reactions were seen in 94 (3.5%) patients. Due to missing data in the file, 81 patients were included in the study. 44 (54.3%) of the cases were women; mean age (mean ± SD) 50.7 ± 17.69 years; 76 (93.8%) of them are citizens of the Republic of Turkey; 58 (71.6%) of them were diagnosed bacteriologically; 65 (80.2%) of them were pulmonary tuberculosis. The most common skin finding was urticaria in 49 (60.5%). The drug responsible for the most common reaction was pyrazinamide. In 49 (60.5%) cases, drugs were given by desensitization and it was successful. The duration of treatment was 7.91 ± 2.5 months (6-18 months). When evaluated in terms of treatment results, 68 (84%) patients successfully completed the treatment. CONCLUSION: Our study is the largest series of patients who developed type 1 immediate hypersensitivity reaction while receiving antituberculosis treatment. A practical, easy desensitization scheme has been shared.

Relationships between quality of life, sleep problems, and sleep quality in patients with chronic idiopathic urticaria.

BACKGROUND: In this study, we aimed to evaluate the sleep quality among chronic urticaria patients using the Chronic Urticaria Quality-of-Life Questionnaire (CU-Q2oL), sleep quality assessment tools, and polysomnography and to investigate any relationships between the obtained results. METHODS: The study included 21 patients diagnosed with chronic spontaneous urticaria and 19 healthy controls. We recorded the patients' sleep quality data, including CU-Q2 oL, Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and polysomnography results. RESULT: Patients in the chronic urticaria group were more likely to have an ESS score of ≥10 (52.4% vs. 5.3%, p = 0.004) and an apnea-hypopnea index of ≥5 (44.4% vs. 5.3%, p = 0.017) compared to the control group. In the patient group, the CU-Q2 oL total score was positively correlated with sleep latency (r = 0.713, p = 0.004) and PSQI-C1 score (r = 0.726, p = 0.005), while it was negatively correlated with urticaria duration (r = -0.579, p = 0.015), apnea-hypopnea index (r = -0.607, p = 0.021), longest apnea duration (r = -0.583, p = 0.029), total number of respiratory events (r = -0.618, p = 0.018), and apnea count (r = -0.686, p = 0.007). CONCLUSION: We conclude that sleep-related problems exist among a considerably large proportion of patients with chronic spontaneous urticaria.

Nasal eosinophilia can predict bronchial hyperresponsiveness in persistent rhinitis: evidence for united airways disease concept.

BACKGROUND: Nasal eosinophils may be indicative of bronchial hyperresponsiveness (BHR) in rhinitis concerning the "united airways disease" theory. This study was designed to evaluate the relationship between nasal eosinophilia and BHR in persistent perennial rhinitis patients. METHODS: Thirty-seven patients (12 males and 25 females, mean age: 33.3 ± 10.4 years) were included in the study. Skin-prick test, nasal symptom score, nasal smears, methacholine bronchial challenge test, and nasal rhinometry were obtained in all patients. Eosinophil count in nasal smears was expressed as a percentage of the total cells. None of the patients had asthma. RESULTS: There was no difference between the number of atopic and nonatopic patients having BHR (4/20 versus 4/17; chi-squared = 0.07; p > 0.05). Total nasal flow was lower and percentage of nasal eosinophils was higher in the patients with BHR than in patients without BHR (p = 0.012 and p = 0.009, respectively). A cutoff point of 68% nasal eosinophils yielded a sensitivity of 100% (63.1-100) and a specificity of 58.6% (38.9-76.5) to determine the presence of BHR. Positive likelihood ratio for the value of eosinophils above cutoff value was 2.42 (1.8-3.3). CONCLUSION: This study shows the relationship between nasal eosinophils and BHR in persistent perennial rhinitis patients. Nasal eosinophil percentage below cutoff value indicates that a patient does not have BHR.

Autologous serum skin test response in chronic spontaneous urticaria and respiratory diseases and its relationship with serum interleukin-18 level.

Autologous serum skin test (ASST) is mostly used in chronic spontaneous urticaria (CSU) to show autoreactivity. Interleukin-18 (IL-18) has also been shown to be involved in autoimmune conditions. To investigate the role of autoreactivity assessed by ASST in CSU and respiratory diseases and to investigate whether this autoreactive state is related to IL-18 level or other clinical covariates. Fifty-five patients with CSU (mean age: 40.3 ± 12.3 years), 70 patients with persistent asthma (mean age: 43.7 ± 9.6 years), 21 patients with seasonal allergic rhinitis (SAR) (mean age: 35.5 ± 11.8 years) and 20 normal controls (mean age: 37.7 ± 9.8) were included. All subjects underwent a laboratory examination and skin prick test. ASST was performed and serum IL-18 levels were measured in all subjects. Positive response to ASST and serum IL-18 levels were higher in CSU patients than those with respiratory diseases (asthma and SAR) (P = 0.034 and 0.002, respectively) and normal controls (P = 0.004 and 0.031, respectively). Considering all patients, IL-18 levels were higher in patients with positive ASST (301.8 ± 194.4 vs. 241.8 ± 206.3 pg/ml, P = 0.036) than ASST negative patients. ASST response was associated with disease severity in CSU (P = 0.037) and asthma patients (P = 0.001). Multivariate analysis showed that positive response to ASST was significantly associated with diagnosis of CSU (OR: 3.13, 95% CI: 1.25-7.87) and female gender (OR: 3.98, 95% CI: 1.19-13.38). ASST response could be related with activity of the disease. A positive ASST response found in respiratory diseases patients suggests that it may occur as a result of some inflammatory events during the diseases' process.