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.

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.

Pulmonary alterations in patients with chronic HCV infection.

BACKGROUND: Chronic hepatitis C virus infection has been reported in association with several extrahepatic manifestations. Included in this list is interstitial lung involvement. AIMS: The aim of the present study was to evaluate pulmonary alterations in patients with chronic hepatitis C virus infection. PATIENTS: Twenty-one patients with chronic hepatitis C virus infection were enrolled into a prospective study. One patient has been excluded because of underlying tuberculosis. METHODS: All patients underwent pulmonary function tests, diffusion capacity for carbon monoxide and high-resolution computed tomography of the chest. RESULTS: Forced vital capacity, forced expiratory volume in first second/forced vital capacity and forced expiratory volume in first second values were reduced to less than 80% of predicted values in 3, 11 and 5 patients, respectively. Diffusion capacity for carbon monoxide was low in 12 patients (60%), 8 of whom had simultaneous decrease in diffusion capacity for carbon monoxide/VA values. Thorax high-resolution computed tomography revealed abnormal findings in eight patients (40%). Fifteen patients with chronic hepatitis C virus infection (75%) had at least one pulmonary alteration as evidenced by abnormal pulmonary function tests, diffusion capacity for carbon monoxide and/or high-resolution computed tomography results. CONCLUSION: In spite of a limited study population, these findings may implicate that pulmonary manifestations of chronic hepatitis C virus infection are frequently underdiagnosed.

The safety of allergen immunotherapy (IT) in Turkey.

Allergen immunotherapy (IT) has encouraging therapeutic outcomes but its safety is still being questioned because of possible severe systemic reactions. The aim of this study was to determine the frequency of systemic reactions (SR), and to identify their correlation with the characteristics of therapy, such as allergen composition and IT schedule, and diagnosis. We analyzed the data of 126 patients who received IT between 2000-2003, and suffered from respiratory allergy or hymenoptera venom anaphylaxis. IT was given by rush, clustered or conventional schedules. The standardized allergen extracts used were grass pollen, house dust mite and hymenoptera venom in 88, 18 and 20 patients, respectively. None of the patients received premedication. A total 4705 injections were administered. One hundred and twenty-three adverse events (AE) (2.6% per injection) were documented in 46 patients. Sixty-one of them were SRs (1.3% SRs per injection) and they were seen in 28 patients. Asthmatics had more tendency to SRs (p=0.05). Rush (1.8%) and clustered (2.8%) IT protocols were associated with a higher rate of SRs (per injection) when compared to conventional schedule (0.9%) (rush vs conventional; p=0.013, clustered vs conventional; p=0.001). The majority of SRs corresponded to grade 3 (49%). Forty-nine (80%) of the 61 SRs were observed during the build-up phase, and mostly with pollen extracts (75.5%). Patients showed more severe SRs during the build-up phase (p<0.05). Twenty-six (42.6%) of the SRs were immediate, whereas 35 (57.4%) SRs appeared within 2 hours. Delayed SRs were significantly more frequent in polysensitized patients when compared to monosensitized subjects (p=0.018). Our data indicate that rapid IT regimens and the presence of asthma represent a greater risk for SR development. Since the late SRs occur as frequently as the early ones, we suggest a longer waiting period beyond 30 minutes, especially in polysensitized and asthmatic patients.

Breast tuberculosis.

Breast tuberculosis is a rare form of tuberculosis. Of all the breast diseases treated surgically, tuberculosis is seen in the range between 0.025% and 0.1%. This ratio is higher in undeveloped countries. We presented five cases with breast tuberculosis. Their ages were between 20 and 63 years. All of them had children and were breastfeeding. The cause of admission to the hospital was swelling in four of them and pain in the remainder. All of the lesions were unilateral. One case had received antituberculosis treatment for pulmonary tuberculosis 10 years ago. AAFB was not detected in sputum, breast discharge, urine and tissue culture in all the cases. Diagnosis was made histopathologically from the excisional biopsy material. Caseating granulomatosis was also found in axillary lymph nodes in three cases. Antituberculosis therapy was planned as 2HRZE/4HR for all of the cases. Three of them completed the therapy without any complaints. One case left the hospital without permission. The last one is now undergoing resistant tuberculosis treatment for pulmonary disease without any complaint of her breast. As a conclusion, although tuberculosis of breast is extremely rare, it should be kept in mind particularly in developing and undeveloped countries.