Cutaneous drug reactions to antiepileptic drugs and relation with HLA alleles in the Turkish population.

Summary: Background and objective. Many studies have shown associations between HLAB*15:02, HLA-A*31:01 and carbamazepine (CBZ)-induced delayed cutaneous hypersensitivity reactions. The aim of this study is to evaluate a possible association between delayed cutaneous reactions to antiepileptic drugs (AEDs) and certain HLA-A and HLA-B alleles in the Turkish population. Methods. The study consisted of 3 groups: Group I (reactive group) included the patients who had documented delayed cutaneous reactions to any antiepileptic drug. Group II (non-reactive group) included the patients who have been on antiepileptic treatment at least for three months without any adverse reactions. Group III consisted of healthy subjects. The HLA-A and B alleles were analyzed in all groups. Results. Forty patients (29 female) had experienced different hypersensitivity reactions due to AEDs: maculopapular exanthema (26 patients), Stevens-Johnson syndrome (6 patients), drug rash with eosinophilia and systemic symptoms (7 patients), toxic epidermal necrolysis (1 patient). Lamotrigine (11) and CBZ (10) were the most common culprit drugs involved in the reactions. The HLA-B*15:02 was not present in any of the study groups. However, HLA-B*35:02 was found in 4 patients from the reactive group, while it was not observed in non-reactive patients and was detected in only one healthy subject (p = 0.021). Conclusion. Although our preliminary results did not indicate a strong allele association with AED hypersensitivity, HLA-B*35:02 appears to be a candidate allele for MPE / DRESS / DIHSS induced by AED's in Turkish population. Further studies with a larger sample size may result in more comprehensive data about the genetic tendency for AED hypersensitivity in the Turkish population.

Evaluation of hypersensitivity reactions to nonsteroidal anti-inflammatory drugs according to the latest classification.

BACKGROUND/AIM: The consensus document for hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) proposed by the European Network for Drug Allergy (ENDA) interest group (2011) was revised in 2013. We aimed to evaluate the usability of the latest NSAID hypersensitivity classification of ENDA. METHOD: A total of 370 patients with a history of hypersensitivity reactions to NSAIDs among the 1250 outpatients referred for suspected drug allergy between July 2013 and June 2014 were evaluated, and 308 patients who were confirmed as having NSAID hypersensitivity were included in this study. After confirming the diagnosis, a single-blind placebo-controlled drug provocation test was performed with aspirin or diclofenac to categorize the patients according to the ENDA classification. The reactions not meeting the ENDA classification criteria were grouped as blended reactions. RESULTS: Among the 308 patients (224 female, mean age 42.12 ± 13.24), the leading cause of hypersensitivity reactions was metamizol (30.5%) followed by aspirin (30.2%). The most common NSAID hypersensitivity subgroup was SNIUAA (46.4%) and the least common type was SNIDR (1.6%). Cross-reactivity was identified in 50.3% of the patients. In five patients (1.6%), the hypersensitivity reactions to NSAIDs did not meet the ENDA classification: Three patients experienced anaphylaxis with different NSAIDs, one patient encountered anaphylaxis with one NSAID and urticaria with other NSAIDs, and the last patient had angioedema with different NSAIDs. CONCLUSION: The latest ENDA classification for NSAID hypersensitivity is generally a practical and useful instrument for clinicians. We only point out that anaphylaxis with different NSAIDs can be seen in a small group of patients.

Drug allergy in tertiary care in Turkey: results of a national survey. The ADAPT study: adult drug allergy perception in Turkey.

BACKGROUND: No data are available on the incidence of drug hypersensitivity (DH) reactions in outpatient settings of tertiary allergy/immunology clinics. Our aims were to document the frequency of outpatient hospital admissions due to DH reactions to allergy/immunology clinics in adults and the management of these reactions in real life. We also investigated whether drug allergy affected social and medical behaviours of the patients. METHODS: This multi-centre study was performed for one year with the participation of 11 out of 16 tertiary allergy/clinical immunology clinics in Turkey. The study group consisted of the patients with DH reactions. Results of a questionnaire including drug reactions and management were recorded. RESULTS: Among 54,863 patients, 1000 patients with DH were enrolled with a median of 2.1% of all admissions. In real life conditions, the majority of approaches were performed for finding safe alternatives (65.5%; 1102 out of 1683) with 11.7% positivity. Diagnostic procedures were positive in 27% (154/581) of the patients. The majority of the patients had higher VAS scores for anxiety. A total of 250 subjects (25%) reported that they delayed some medical procedures because of DH. CONCLUSION: Our results documented the frequency of admissions due to DH reactions to allergy/clinical immunology clinics for the first time. Although physicians mostly preferred to perform drug tests in order to find safe alternatives, considering the fact that DH was confirmed in 27% of the patients, use of diagnostic tests should be encouraged, if no contraindication exists in order to avoid mislabelling patients as DH.

Immediate-type hypersensitivity reactions to proton pump inhibitors: usefulness of skin tests in the diagnosis and assessment of cross-reactivity.

BACKGROUND: Data are limited about the value of skin tests in the diagnosis of proton pump inhibitor (PPI)-induced hypersensitivity reactions and the cross-reactivity between PPIs. We aimed to assess the role of skin testing in the diagnosis of PPI-related immediate hypersensitivity reactions and the cross-reactivity patterns among PPIs. METHODS: The study was designed in a prospective, national, multicentre nature. Sixty-five patients with a suggestive history of a PPI-induced immediate hypersensitivity reaction and 30 control subjects were included. Standardized skin prick and intradermal tests were carried out with a panel of PPIs. Single-blind, placebo-controlled oral provocation tests (OPTs) with the PPIs other than the culprit PPI that displayed negative results in skin tests (n = 61) and diagnostic OPTs with the suspected PPI (n = 12) were performed. RESULTS: The suspected PPIs were lansoprazole (n = 52), esomeprazole (n = 11), pantoprazole (n = 9), rabeprazole (n = 2), and omeprazole (n = 1). The sensitivity, specificity, and negative and positive predictive values of the skin tests with PPIs were 58.8%, 100%, 70.8%, and 100%, respectively. Fifteen of the 31 patients with a hypersensitivity reaction to lansoprazole had a positive OPT or skin test result with at least one of the alternative PPIs (8/52 pantoprazole, 6/52 omeprazole, 5/52 esomeprazole, 3/52 rabeprazole). CONCLUSION: Considering the high specificity, skin testing seems to be a useful method for the diagnosis of immediate-type hypersensitivity reactions to PPIs and for the evaluation of cross-reactivity among PPIs. However, OPT should be performed in case of negativity on skin tests.

Methotrexate: can it be a choice for nasal polyposis in aspirin exacerbated respiratory disease?

Nasal polyposis (NP) is considered a subgroup of chronic rhinosinusitis and is commonly associated with asthma, bronchiectasis, and cystic fibrosis. A certain subgroup of nasal polyposis is known as Aspirin Exacerbated Respiratory Disease (AERD), previously called Samter's Triad or aspirin triad, comprising polyposis, asthma, and aspirin hypersensitivity and makes up almost 10% of cases of NP. Therapy of NP involves a combination of medical and surgical treatments. However, recurrences are common, particularly in patients with asthma and aspirin hypersensitivity. Both topical and systemic corticosteroids form the mainstay of conservative therapy for NP as well as a primary treatment and prevention for recurrences. They have been shown to improve nasal breathing, rhinitis symptoms, and reduce the size of NP, along with the rate of recurrence. There is great concern about the adverse effects of systemic steroids, especially when long-term usage is necessary to maintain improvement. So far, no knowledge exists about the effects of methotrexate (MTX) on NP of the patients with asthma. We report two patients whose NP dramatically reduced in size after a course of MTX therapy administered as an additional treatment for their steroid- dependent asthma.

Revised dental beliefs survey: reliability and validity of a 22-item modified Turkish version.

The aim of this study is to create a Turkish version of the Revised Dental Beliefs Survey (DBS-R) and describe its psychometric properties. The participants were 420 general dental patients. The results of the exploratory factor analysis revealed that the DBS-R consisted of three factors consisting of 22 items. Confirmatory factor analysis results showed that the 22-item three-factor version fit the data better than the original 28-item English language four-factor structure model proposed in Odontol Scand (2004;62:21). The internal reliability of the Turkish version of the DBS-R was Cronbach alpha of 0.88. The correlation between the Turkish version of the DBS-R and the Modified Dental Anxiety Scale (MDAS) was 0.29. Scores on the 22-item version were higher for anxious participants (MDAS > or = 15) than those determined to be not anxious [59.4 +/- 15.5 vs. 51.1 +/- 17.2 (t = -4.38, P < 0.0001)]. In conclusion, a 22-item modified version of the DBS-R in Turkish appears reliable and valid.

Confirmed prevalence of food allergy and non-allergic food hypersensitivity in a Mediterranean population.

BACKGROUND: Until the present, no comprehensive studies evaluating the prevalence of food allergy and non-allergic food hypersensitivity (FA/NAFH) in adults have been done in Turkey or its surrounding countries. OBJECTIVE: This large population-based study was planned to identify the confirmed prevalence of adverse reactions to food in adults in Istanbul. METHODS: A total of 17 064 telephone numbers were randomly selected from both the European and Asian sides of Istanbul, and the 11 816 subjects who agreed to participate in the study were addressed with a questionnaire of eight items. Those who disclosed food-related complaints in this survey were called again and a similar questionnaire was repeated. The respondents who were suspected of having food allergy or food hypersensitivity were invited for a personal clinical investigation that included double-blind, placebo-controlled food challenge tests. RESULTS: The lifetime prevalence of self-reported FA/NAFH was found to be 9.5% [1118/11 816; 95% confidence interval (CI): 8.94-10.00%]. After the clinical investigations, the point prevalence of FA/NAFH, which also included the 'possible FA/NAFH group', was found to be as low as 0.3% (30/11 816; 95% CI: 0.17-0.36%), and the FA/NAFH rates assessed by double-blind, placebo-controlled food challenge tests were 0.1% (12/11 816; 95% CI: 0.05-0.18%) and 0.1% (11/11 816; 95% CI: 0.05-0.17%), respectively. The most significant factor influencing FA/NAFH was familial atopy (adjusted OR 4.3; 95% CI: 3.67-4.99), and the most related atopic disease was itching dermatitis/urticaria (adjusted OR: 3.9; 95% CI: 3.31-4.54). CONCLUSION: We may conclude that FA/NAFH in the Turkish population seems to be low when compared with Northern and Western European countries. This may be due to genetic, cultural or dietary factors, and further studies evaluating the reasons for this low prevalence of FA/NAFH in our population are needed.

Hashimoto thyroiditis and obstructive sleep apnea syndrome: is there any relation between them?

Hashimoto thyroiditis (HT), which is an autoimmune disease of thyroid gland, has been declared to present with concomitant several systemic diseases. In this study, the coexistence of the Hashimoto disease with the sleep apnea syndrome has been examined. Seven female patients (33-66 year of age) with Hashimoto thyroiditis were evaluated for sleep apnea syndrome. The diagnosis of Hashimoto disease was based on the high titers of anti-thyroid antibodies and histological findings. None of the patients had any complaints of sleep disturbances. Seven healthy subjects with similar age and sex characteristics were taken as the control group. All the patients and the control subjects were undertaken a full polysomnography (PSG). Five patients with HT showed the characteristics of obstructive sleep apnea syndrome (one severe, one moderate and three mild OSAS), whereas no sleep breathing disturbance was found in the control group. These findings suggest that sleep related breathing problems may develop in the patients with autoimmune thyroiditis even if they are euthyroid.

Successful desensitization to vitamin D in a patient with vitamin D deficiency

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Successful capecitabine desensitization for a delayed-type hypersensitivity reaction

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A study of serological markers of hepatitis B and C viruses in Istanbul, Turkey.

OBJECTIVE: This study was undertaken to investigate the prevalence of HBsAg, anti-HBs and anti-HCV positivity in Istanbul, Turkey. SUBJECTS AND METHODS: The frequencies of HBsAg, anti-HBs and anti-HCV positivity were determined in 1,157 randomly selected patients attending the outpatient clinic of Istanbul University Hospital, Istanbul, Turkey, during the years 1998 and 2001. All patients underwent complete physical and various routine laboratory examinations. RESULTS: Of the 1,157 patients, the prevalence of HBsAg, anti-HBs and anti-HCV was 6.6, 28.1 and 2.4%, respectively. It appeared that having dental and surgical procedures formed the risk factors for HBV infection. HBsAg positivity in the health care workers was not different from that of the other professions, but anti-HBs was significantly higher in this group. CONCLUSIONS: Our findings indicate that HBV infection occurs more frequently than HCV in Istanbul, and this poses an important health problem in the community.

Evaluation of the effect of low-dose oral theophylline therapy on some bone turnover markers and serum prolidase I activity in mild asthmatics.

Hypercalcemia and hypercalciuria observed both in humans and in animals who were on long-term theophylline therapy, prompted us to investigate whether oral theophylline treatment at optimal doses causes any adverse side effects on bone metabolism in mild asthmatics. Therefore, serum osteocalcin (BGP) and total alkaline phosphatase (TALP, EC 3.1.3.1) as bone formation markers, serum prolidase I (EC 3.4.13.9) activity as a marker for collagen metabolism, urinary deoxypyridinoline (Dpd), hydroxyproline (Hyp) and fasting urinary calcium as bone resorption markers, were measured in 18 mild asthmatics who had been treated with theophylline over 1-10 years. Among measured bone turnover markers, BGP, TALP, and Hyp levels were found to be increased in mild asthmatics; and BGP showed the greatest percent mean increase (98%) over the healthy subjects. However, these increments did not exceed the upper reference limits. Serum prolidase I activity was also increased in mild asthmatics receiving theophylline. Our results indicate that theophylline therapy at optimal doses may not exert adverse side effects on bone homeostasis, but patients receiving supratherapeutic doses of theophylline should be under close examination in order to predict future bone mass status.

Drug allergy in tertiary care in Turkey: Results of a national survey. The ADAPT study: Adult drug allergy perception in Turkey

BACKGROUND: No data are available on the incidence of drug hypersensitivity (DH) reactions in outpatient settings of tertiary allergy/immunology clinics. Our aims were to document the frequency of outpatient hospital admissions due to DH reactions to allergy/immunology clinics in adults and the management of these reactions in real life. We also investigated whether drug allergy affected social and medical behaviours of the patients. METHODS: This multi-centre study was performed for one year with the participation of 11 out of 16 tertiary allergy/clinical immunology clinics in Turkey. The study group consisted of the patients with DH reactions. Results of a questionnaire including drug reactions and management were recorded. RESULTS: Among 54,863 patients, 1000 patients with DH were enrolled with a median of 2.1% of all admissions. In real life conditions, the majority of approaches were performed for finding safe alternatives (65.5%; 1102 out of 1683) with 11.7% positivity. Diagnostic procedures were positive in 27% (154/581) of the patients. The majority of the patients had higher VAS scores for anxiety. A total of 250 subjects (25%) reported that they delayed some medical procedures because of DH. CONCLUSION: Our results documented the frequency of admissions due to DH reactions to allergy/clinical immunology clinics for the first time. Although physicians mostly preferred to perform drug tests in order to find safe alternatives, considering the fact that DH was confirmed in 27% of the patients, use of diagnostic tests should be encouraged, if no contraindication exists in order to avoid mislabelling patients as DH

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