Ozlem Goksel

Hypersensitivity Reactions to Contrast Media: Prevalence, Risk Factors and the Role of Skin Tests in Diagnosis – A Cross-Sectional Survey

Background: Hypersensitivity to contrast media (CMs) may be common and serious. Aim: To evaluate the prevalence of CM hypersensitivity, risk factors associated with it and the role of skin testing in its diagnosis. Methods: A structured questionnaire was administered to patients who underwent computed tomography during a 1-year period. Skin tests with CMs, including skin prick tests (SPTs), intradermal tests (IDTs) and patch tests (PTs), were conducted on CM reactors (n = 24). Volunteers who tolerated CM exposure or had never been exposed to any CMs served as controls (n = 37). Results: A total of 1,131 patients (630 females and 501 males; mean age 55 ± 14.2 years) were enrolled in the study. The prevalence of historical and current CM reactors was 33/1,131 (2.92%) and 8/1,105 (0.72%), respectively. The skin was the most affected site, with mild to moderate reactions. Female gender, a history of doctor-diagnosed asthma, drug allergy, food allergy and psychiatric diseases were significant risk factors. The sensitivities of SPTs and early readings of IDTs in the diagnosis of immediate reactions were 0 and 20%, respectively, and the specificities were 94.6 and 91.4%, respectively. For early readings of IDTs, the positive predictive value (PPV) and negative predictive value (NPV) were 40 and 80%, respectively. For nonimmediate reactions, the sensitivities of delayed readings of IDTs and PTs were 14.3 and 25%, respectively; specificity was 100% for both tests. The PPV was 100% for both of these tests, and the NPVs were 85.4 and 82.4%, respectively. Conclusions: Our findings are comparable with the incidence, profile and risk factors associated with CM hypersensitivity reported previously. Skin testing with CMs has a high specificity, but its role in diagnosis is limited due to low sensitivity.

Successful Colchicine Therapy in a Patient With Follicular Bronchiolitis Presumed to Be Asthma

Follicular bronchiolitis (FB) is a rare small-airway pathology that is associated mainly with connective tissue diseases. This case report presents a new, diagnosed, different airway disease in a non-smoker with rheumatoid arthritis in remission who was treated for presumed asthma, but was not controlled. She was ultimately diagnosed with FB after video-assisted thoracoscopic surgery. The clinical findings of FB were controlled successfully by colchicine after she did not respond to systemic steroid therapy. This is the first case report of FB associated with rheumatoid arthritis that responded to colchicine.

Prevalence and significance of MEFV gene mutations in patients with sarcoidosis

Objectives: Sarcoidosis is a chronic granulomatous disease. Pyrin has anti-inflammatory activity in the regulation of inflammasomes and is encoded by the Mediterranean fever (MEFV) gene. MEFV gene mutations trigger the inflammatory cascade and cause familial Mediterranean fever (FMF). A relationship between various rheumatic diseases and MEFV gene mutations has been demonstrated. The aim of this study was to determine the prevalence of the MEFV gene mutation in Turkish patients with sarcoidosis and to detect any possible correlation with disease phenotype. Method: The study included 78 sarcoidosis patients and 85 healthy subjects matched for age, gender, and ethnicity. MEFV gene mutations were investigated with the FMF strip assay, which is based on reverse hybridization of biotinylated polymerase chain reaction (PCR) products. Results: Of the 78 patients with sarcoidosis, nine (11.5%) were found to be carriers of MEFV gene mutations. The distribution of these nine mutations were: three (3.8%) V726A, two (2.5%) E148Q, two (2.5%) M680I, one (1.3%) A744S, and one (1.3%) K695R. Carriers of M694V, M694I, R761H, and P369S were not detected in any of the sarcoidosis patients. None of the sarcoidosis patients were found to be compound heterozygous carriers. The prevalence of the MEFV gene mutation carrier detected in the healthy control group was 22.4%. The distribution of the 19 MEFV gene mutations found in the healthy controls was: nine (10.6%) E148Q, two (2.3%) M694V, one (1.2%) M694I, one (1.2%) M680I, two (2.3%) V726A, one (1.2%) A744S, two (2.3%) K695R, and one (1.2%) P369S. When compared with the control group, a lower prevalence of the MEFV gene mutation carrier was found in sarcoidosis patients but this was not statistically significant (p = 0.067). In nine patients found to be MEFV gene mutation carriers, higher serum erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels and higher numbers patients with arthritis, enthesitis, and ankle arthritis were found (p = 0.01, p = 0.04, p = 0.028, p = 0.05, p = 0.05, respectively). Conclusions: When we compared Turkish sarcoidosis patients with the healthy control group, we found a lower prevalence of MEFV gene mutations. In sarcoidosis patients, the MEFV gene mutation carrier was found to be related to high acute-phase responses, arthritis, and enthesitis. The existence of MEFV gene mutations may have a preventive role with regard to the development of sarcoidosis. Prospective studies that include larger patient populations are needed.

Long-Term Omalizumab Treatment: A Multicenter, Real-Life, 5-Year Trial

Background: Omalizumab has demonstrated therapeutic benefits both in controlled clinical trials and real-life studies. However, research concerning the long-term effects and tolerability of omalizumab is needed. The main objective of this study was to evaluate the effectiveness and tolerability of treatment with omalizumab for up to 5 years. Methods: A multicenter, retrospective, chart-based study was carried out to compare documented exacerbations, hospitalizations, systemic steroid requirement, FEV1, and asthma control test (ACT) results during 1 year prior to omalizumab treatment versus at 1, 3, and 5 years of treatment. Adverse events and reasons for discontinuation were also recorded at each time point. Results: Four hundred and sixty-five patients were enrolled in the study. Outcome variables had improved after the 1st year and were sustained after the 3rd and 5th years of treatment with omalizumab. Omalizumab treatment reduced the asthma exacerbation rate by 71.3% (p < 0.001) at 1 year, 64.3% (p < 0.001) at 3 years, and 54.8% (p = 0.002) at 5 years. The hospitalization rate also decreased; by the 5th year of the treatment no patients were hospitalized. ACT results had also improved significantly: 12 (p < 0.001) at 1 year, 12 (p < 0.001) at 3 years, and 12 (p = 0.002) at 5 years. Overall, 12.7% of patients reported adverse events (most of these were mild-to-moderate) and the overall dropout rate was 9.0%. Conclusion: Omalizumab had a significant effect on asthma outcomes and this effect was maintained over 5 years. The drug was found to be generally safe and treatment compliance was good.

What is the clinical value of negative predictive values of skin tests to iodinated contrast media

BACKGROUND Iodinated contrast media (ICM) can cause hypersensitivity reactions (HSR), yet data are scant about the negative predictive value (NPV) of ICM skin tests. OBJECTIVE To determine the NPV of skin tests to ICM Methods: We enrolled 73 patients with a history of HSRs to ICM, 136 subjects with no previous exposure to ICM, and, as controls, 47 subjects who had previously tolerated ICM. All the subjects had skin tests with the culprit and/or alternative ICM and were later questioned as to whether they were reexposed and/or reacted to the skin-test-negative ICM. RESULTS Sixty (82.2%) and 13 (17.8%) patients had a history of immediate HSR and those with a history of nonimmediate HSR, respectively. The sensitivity and specificity of the skin tests were 18% and 97%, respectively, in patients with immediate HSR and were 23% and 99%, respectively, in patients with nonimmediate HSR. Of a total of 237 subjects with negative skin test results, 207 (87.3%) were asked about further ICM administration; 158 (84.9%) confirmed subsequent use either with (n = 15 [9.4%]) or without premedication (n = 143 [90.6%]). Of the 143 individuals, 140 tolerated skin-test-negative ICMs but three (1.9%) reacted to ICMs (two with mild nonimmediate reactions, one with a grade 1 immediate reaction). Of 20 patients who had previous HSR to ICM, 17 tolerated further skin-test-negative ICM without premedication. The NPV of ICM skin tests, therefore, was 97% (95% confidence interval, 7599%). CONCLUSION The NPV of skin tests with ICM was high. None of the reactions in patients who had negative skin test results were severe, which may reassure physicians who hesitate to perform further evaluations in patients with negative skin test results.BACKGROUND Iodinated contrast media (ICM) can cause hypersensitivity reactions (HSR), yet data are scant about the negative predictive value (NPV) of ICM skin tests. OBJECTIVE To determine the NPV of skin tests to ICM Methods: We enrolled 73 patients with a history of HSRs to ICM, 136 subjects with no previous exposure to ICM, and, as controls, 47 subjects who had previously tolerated ICM. All the subjects had skin tests with the culprit and/or alternative ICM and were later questioned as to whether they were reexposed and/or reacted to the skin-test-negative ICM. RESULTS Sixty (82.2%) and 13 (17.8%) patients had a history of immediate HSR and those with a history of nonimmediate HSR, respectively. The sensitivity and specificity of the skin tests were 18% and 97%, respectively, in patients with immediate HSR and were 23% and 99%, respectively, in patients with nonimmediate HSR. Of a total of 237 subjects with negative skin test results, 207 (87.3%) were asked about further ICM administration; 158 (84.9%) confirmed subsequent use either with (n = 15 [9.4%]) or without premedication (n = 143 [90.6%]). Of the 143 individuals, 140 tolerated skin-test-negative ICMs but three (1.9%) reacted to ICMs (two with mild nonimmediate reactions, one with a grade 1 immediate reaction). Of 20 patients who had previous HSR to ICM, 17 tolerated further skin-test-negative ICM without premedication. The NPV of ICM skin tests, therefore, was 97% (95% confidence interval, 75-99%). CONCLUSION The NPV of skin tests with ICM was high. None of the reactions in patients who had negative skin test results were severe, which may reassure physicians who hesitate to perform further evaluations in patients with negative skin test results.

THU0567 Prevalence and Significance of MEFV Gene Mutations in Patients with Sarcoidosis

Background Sarcoidosis is a chronic granulomatous disease. Pyrin, is encoded by the MEFV gene and has anti-inflammatory effects in the inflammasoma regulation. MEFV gene mutations affects the inflammatory cascade and cause familial Mediterranean fever. The relationship between different rheumatic diseases and MEFV gene mutations are shown in previous studies. Objectives The aim of this study was to determine the MEFV gene prevalence in Turkish patients with sarcoidosis and to determine the possible correlation between the occurrence of mutations and disease phenotype. Methods Seventy-eight sarcoidosis patients and age, gender and ethnicity compatible 85 healthy controls were included in the study. The most common eight MEFV gene mutations were investigated by PCR method. Results Among seventy-eight sarcoidosis patients MEFV gene mutation was detected in nine patients (%11.5). The distribution of the nine mutations were as; three (3.8%) V726A, two (2.5%) E148Q, two (2.5%) M680, one (1.3%) A744S, one (1.3%) K695, respectively. None of the sarcoidosis patients were M694V, M694I, R761H and P369S and compound heterozygous carriers. MEFV gene mutations frequency in the healthy control group was found to be 22.4%.The distribution of MEFV gene mutations in the healthy control were; E148Q 9 (10.6%), M694V 2 (2.3%), M694I 1 (1.2%), M680 1 (1.2%), V726A 2 (2.3%), A744S1 (1.2%), K695 2 (2.3%), P369S1 (1.2%), respectively, Compared with the control group, a lower carrier frequency of MEFV gene mutations were detected in patients with sarcoidosis, but it was not statistically significant (p=0.067). In the sarcoidosis group, while serum ESR and CRP levels were significantly higher in the mutation carrier group than those of the non-carrier group (p=0.01, p=0.04). In the sarcoidosis group, while arthritis,enthesitis and ankle arthritis were significantly more frequent in the mutation carrier group than those of the non-carrier group (p=0.028, p=0.05, p=0.05 respectively). Conclusions We found a lower frequency of MEFV gene mutations in Turkish patients with sarcoidosis compared with healthy control group. Sarcoidosis mutation carrier group were found to be associated with high serum acute phase response, arthritis and enthesitis. The presence of MEFV gene mutation may have a protective role for the development of sarcoidosis. Prospective studies with large patient series are need on this subject References Newman LS, Rose CS, Maier LA. Sarcoidosis. New England Journal of Medicine 1997; 336: 1224±1234. Hofmann S, Franke A, Fischer A, et al. Genome-wide association study identifies ANXA11 as a new susceptibility locus for sarcoidosis. Nat Genet. 2008; 40:1103–1106. Yilmaz E, Ozen S, Balci B, et al. Mutation frequency of Familial MediterraneanFever and evidence for a high carrier rate in the Turkish population. Eur J Hum Genet 2001;9:553–5. Yigit S, Bagci H, Ozkaya O, et al. MEFV mutations in patients with familialMediterranean fever in the Black Sea region of Turkey: Samsun experience.J Rheumatol 2008;35:106–13. Tunca M, Akar S, Hawkins PN, et al. The significance of paired MEFV mutationsin individuals without symptoms of familial Mediterranean fever. Eur J HumGenet 2002;10:786–9. Disclosure of Interest None declared