Objective: In our population the properties of hypersensitivity reactions to antibiotics aren't well studied. The aim of our study is to determine the rate of hypersensitivity reactions to different antibiotics and the appropriate method to find out alternatives.Materials and Methods: 393 patients, self reporting hypersensitivity reactions to drugs within the past year were enrolled. History was taken and the reported reactions to antibiotics were classified. Skin tests with alternative antibiotics were applied. Double-blind placebo controlled drug provocation tests were done to the patients with negative skin test results.Results: 192 (48.9%) patients were determined as having hypersensitivity reactions to antibiotics. These reactions were not associated with atopy, asthma or chronic urticaria. The reported antibiotics were amoxicillin (15.3%), penicillin (12.5%), ampicillin (12%), quinolones (5.9%), 2nd generation cephalosporins (5.3%), clarithromycin (4.8%), sulphonamides (3.6%), clindamycin (2%), 1st generation cephalosporins (2%), 3rd generation cephalosporins (1.5%), gentamycin (1.3%), tetracycli-ne (1.3%), and macrolides (< 1%) respectively. The most frequent reaction was urticaria, followed by anaphylaxis and other skin reactions. Thirty six out of 40 patients, 77 of 82 patients and 35 of 38 patients with negative skin test results due to ciprofloxacin, cefuroxime acetyl and clindamycin were successfully challenged with each drug respectively. Most of the patients reporting hypersensitivity reactions to amoxicillin, ampicillin and penicillin did not react to cefuroxime acetyl (29/31, 22/25, 18/20 patients, respectively) and clindamycin (21/29, 22/24, 15/17 patients, respectively) in challenge tests. None of the patients with negative challenge tests returned to the clinic due to following adverse reactions.Conclusion: In our study population aminopenicillins and penicillin are likely to be the most frequent causes of hypersensitivity reactions and clindamycin and cefuroxime axetyl seem to be safe alternatives. Although skin test results were mostly concordant with double blind placebo controlled drug provocation tests, double-blind placebo controlled drug provocation tests must be applied in all patients as a confirmative diagnostic procedure in antibiotic allergy.

Treatment of chronic urticaria consists of antihistamines as the first-line treatment. For more severe symptoms, combinations can be necessary as well as dose augmentations. The recent guidelines suggest the possibility of using omalizumab in resistant cases, but this therapy is still investigational. We treated two patients with idiopathic recurrent angioedema and 12 patients with chronic spontaneous urticaria (CSU) with omalizumab, who had not benefited from the recommended first-line, second-line and third-line treatments. To evaluate the efficacy of the omalizumab treatment, urticaria activity scores (UAS) and chronic urticaria quality of life (CU-Q2oL) scores were measured at baseline, and at the end of the first and sixth month of the therapy. The dosage and intervals of omalizumab therapy were determined according to the rules suggested for severe asthma treatment. CU-Q2oL scores and UAS displayed significant improvements in all 14 patients. None of the patients reported any adverse effect during the treatment until the submission of this data. Our results show that omalizumab apparently improves CU-Q2oL as well as UAS in treatment-resistant CSU in a real life setting.

Objective: Questioning the quality of life in patients with chronic diseases is important. However questionnaires should be suitable to the structure and habits of the community studied as well as it should be easily understood. Considering the fact that rhinitis adversely affect the quality of life, we developed a rhinitis scale of quality of life, which suits the life style and habits of our population in patients with rhinitis. Material and Method: Scale includes the 28 parameters that are needed to be graded and scored about daily activities, nasal symptoms, and eye complaints, sleep disorders in addition to social and emotional assessment. A total of 163 patients with allergic rhinitis, that applied to Allergy division of Internal Medicine Department of Istanbul Medical School have been included into the study Symptoms scoring has been performed with short form 36 (SF-36) and novel scale at week 0, week 1 and 1 month after treatment. The results of newly developed rhinitis quality of life scale were compared with statistical methods for language validity, reliability, repeatability, reproducibility and sensitivity. Results: Language validity of scale was shown (n=20). Intraclass correlation coefficient (ICC) is 0.8877, Cronbach cilia is 0.94; these values are high and represent the reliability of new scale (control at 1. week without treatment n=38). Although there is a weak correlation between the results of new scale and SF-36 sub parameter scores, these correlations were significant in statistical analysis (n=.103) (validation). New scale was significantly sensitive for determining the pre and post treatment changes (n=103) (z=-7.452, p=0.000). Conclusion: This newly developed scale is practical, easy to be administrated in short periods; also it has sufficient reliability, reproducibility, validity and sensitivity characteristics. We concluded that this scale is suitable for both determining the clinical status and response to treatment in patients with allergic rhinitis.

Anaphylaxis is a serious and probably lethal systemic reaction which occurs instantaneously after exposure to an allergen. It can occur after exposure to various triggers including allergic and non-allergic factors. When a trigger cannot be determined, idiopathic anaphylaxis is considered. In idiopathic anaphylaxis presenting with frequent attacks, long-term prophylaxis with H1 antihistamine and steroid treatment are recommended. Omalizumab, a humanized monoclonal antibody drug which decreases free immunoglobulin E molecules in the circulation, is approved for the treatment of chronic severe persistent allergic asthma. We report a 46-year-old female patient with severe uncontrolled allergic asthma and idiopathic anaphylaxis presenting with attacks of abdominal pain, generalized urticaria, feeling of strangulation in her throat and unconsciousness. Omalizumab at a dose of 375 mg once every 2 weeks was administrated and at the end of 3 months anaphylactic attacks had ceased. At the end of the sixth month of omalizumab therapy, her injection intervals were extended to 4 weeks. After she began experiencing moderate attacks of urticaria and hoarsening, however, initial treatment plan was reestablished. Currently, she has completed her first year of treatment without further attacks.

BackgroundHereditary angioedema is associated either with a deficiency in the amount or in the function of the C1 inhibitor (C1 INH).ObjectiveIn this study the endothelial function of HAE patients was investigated to evaluate the impact of hereditary C1-INH deficiency on atherosclerosis, which has not yet been established before.MethodsA total of 26 patients (14 female, 12 male. Mean age: 38±13) diagnosed with HAE and 30 healthy controls were enrolled in the study. Measurement of coronary flow reserve (CFR) in the left anterior descending coronary artery was performed using transthoracic doppler harmonic echocardiography at baseline and following dipyridamol infusion. The intima-media thickness (IMT) in the carotid artery was measured using an echocardiographic system equipped with 10MHz linear transducer (Vingmed System Five).ResultsThe mean CFR value for the HAE patient group was significantly lower than that of the control group (p<0.001). The mean IMT was not found to be significantly different between the two groups, although it was slightly higher in the HAE patient group. No correlation was found between the CFR and the disease severity scores, nor was it shown between the CFR values and the duration of danazol treatment.ConclusionOur results indicate that there is a microvascular endothelial dysfunction in HAE patients. Although carotid intima media thickness of these patients was not significantly increased, the presence of microvascular endothelial dysfunction might be regarded as an early indicator of a premature atherosclerosis.

Background: No published data presently exist concerning hereditary angioedema (HAE) in Turkey. The aim of the study was to initiate a preliminary multicentric evaluation about HAE and to determine the genetic properties of Turkish patients. Methods: Based on records drawn from four medical centers we identified a total of 70 subjects, belonging to 60 unrelated families, fulfilling clinical and laboratory criteria for diagnosis of HAE with C1 inhibitor deficiency. Ten type I patients, and their first-degree relatives, underwent genetic analysis for HAE. Results: The majority of patients were female (60%), the mean age was 37.7 ± 14.1 years. The mean age at the time of first angioedema symptom was 12.5 ± 9.2 years. Mean time lag between first symptom and diagnosis was 26 ± 14.4 years. All but 3 subjects had HAE type I. Family history of angioedema was present in 75.7% of the cases. Cutaneous swelling was reported by 87.1% of the patients, facial edema by 65%, abdominal symptoms by 74.3% and approximately one half (55.7%) had experienced one or more laryngeal attack. Genetic analysis of 10 families demonstrated that 5 carried a mutation that had never been previously described. Conclusion: We found that the clinical features of Turkish HAE patients were consistent with previously described patterns of this rare disease. The most noteworthy feature identified in the study was a significantly long duration between the first symptom appearance and final diagnosis. Our detection of different mutations in 10 patients confirms the allelic heterogeneity of the disease.

Schnitzler syndrome is a rare cause of urticaria and is defined by monoclonal gammopathy and chronic urticaria or urticarial vasculitis combined by at least two of the following features: fever, arthralgia or arthritis, bone pain, hepato-and/or splenomegaly, palpable lymph nodes, elevated erythrocyte sedimentation rate, and leukocytosis. Although the pathophysiology is not completely evaluated, it usually presents with resistance to corticosteroids and many patients respond to anakinra, an IL-1 receptor antagonist. The mean age of onset is 51, but very few cases have been documented in elderly patients. Here we describe a 79-year-old woman diagnosed as Schnitzler syndrome who fulfilled the diagnostic criteria of the syndrome with multiple mediastinal lymph nodes, fever and arthralgia, bone pain, elevated erythrocyte sedimentation rate, urticarial vasculitis and a IgG kappa monoclonal gammopathy of undetermined significance. On capillary serum protein electrophoresis of the patient with the Capillarys System, the morphology of the.-region was disturbed. Although there wasn't any obvious monoclonal peak on Capillarys (immunotyping), the result was diagnosed as an IgG kappa type monoclonal immunoglobulin. For the confirmation of our finding we performed immunofixation electrophoresis which is accepted as the gold standard method for the characterization of monoclonal proteins, although it failed to detect an IgG kappa type band. Both kappa and lambda free light chain concentrations were within the reference range, however the kappa/lambda ratio was abnormal. The patient initially responded well to corticosteroids, but later needed to be treated with azathioprine as a corticosteroid sparing drug. After total clinical improvement methylprednisolone was discontinued with tapering and azathioprine was kept on. At the end of 3 months of therapy, she was accepted to be in clinical remission. During her follow up she has remained in remission approximately for a year with the low dose of azothiopurine.

Background: Complete avoidance sometimes cannot be possible in latex-allergic health care workers. So far, very few double-blind placebo-controlled studies revealed the efficacy of sublingual latex immunotherapy (SLIT) in those patients.Objective: Our aim was to evaluate the efficacy and safety of latex SLIT in health care workers.Methods: 30 patients (all health care workers) diagnosed as latex allergic were advised to avoid latex exposure and were given information about the prevention measures and asked to return two months later. 24 patients who were still symptomatic despite prevention measures were informed about the latex SLIT study and asked to participate. However, only 12 gave approval and were randomized to receive sublingual latex extract or placebo. Symptom scores and latex cutaneous provocation test scores were recorded at baseline and at the 6th and 12th months of the study.Results: Two patients experienced anaphylaxis, 1 patient showed severe bronchial obstruction during dose incremental phase and were excluded from the study. The differences of the symptom and provocation scores between baseline and the 12th month of the treatment were significant in the active group (p = .042, p = .038, respectively). Also the symptom and provocation scores at 12 months were significantly lower in the active group than in the placebo group (p = .035, p = .013, respectively).Conclusion: Latex SLIT can be used as an effective treatment for latex-allergic health care patients having difficulties in applying adequate avoidance measures. However, the risk of systemic reactions should be kept in mind and sufficient precaution measures must be made available. Ann Allergy Asthma Immunol. 2010;104:339-342.

To the Editor: Hereditary angioedema (HAE; Online Mendelian Inheritance in Man no. 106100) is a well-defined autosomal dominant trait presented with 3 variants. Type I (HAE-I) and type II (HAE-II) are associated either with a deficiency in or a nonfunctional C1 inhibitor (C1Inh) enzyme, and type III is associated with a different scope of display recently related with the impairment of Factor XII, as noted by Dewald and Bork.1Dewald G. Bork K. Missense mutations in the coagulation factor XII (Hageman factor) gene in hereditary angioedema with normal C1 inhibitor.Biochem Biophys Res Commun. 2006; 343: 1286-1289Crossref PubMed Scopus (323) Google Scholar The genetic cause of C1Inh deficiency shows a very high allelic heterogeneity on the C1 inhibitor gene (C1INH), as noted by Tosi,2Tosi M. Molecular genetics of C1 inhibitor.Review. Immunobiology. 1998; 199: 358-365Crossref PubMed Scopus (125) Google Scholar and more than 250 dominant mutations have been described thus far, including in the recent publication by Pappalardo et al.3Pappalardo E. Caccia S. Suffritti C. Tordai A. Zingale L.C. Cicardi M. Mutation screening of C1 inhibitor gene in 108 unrelated families with hereditary angioedema: functional and structural correlates.Mol Immunol. 2008; 45: 3536-3544Crossref PubMed Scopus (105) Google Scholar Autosomal recessive inheritance is very infrequent and accounted for by the homozygous mutations in the promoter region of the gene as noted by Verpy et al.4Verpy E. Biasotto M. Brai M. Misiano G. Meo T. Tosi M. Exhaustive mutation scanning by fluorescence-assisted mismatch analysis discloses new genotype-phenotype correlations in angioedema.Am J Hum Genet. 1996; 59: 308-319PubMed Google Scholar The proband (Fig 1, A, II:3) was a 53-year-old woman whose symptoms began at the age of 8 years. Since then, she has experienced frequent angioedema attacks. The symptoms randomly affected her face, neck, or extremities and required an emergency treatment at least once a year for severe laryngeal edema. Her 2 sisters had similar clinical findings, both having their first attacks at comparable ages with their sibling (Fig 1, A, II:1 and II:5). Family history revealed no other affected individuals. Routine blood biochemistry analysis of the proband showed normal C1q and C3 levels but decreased levels of C4 and C1Inh, with a decreased C1Inh enzyme activity. Complement profiles of the 2 symptomatic sisters were similar to that of the proband (Table 1). The C1Inh activities of the nonsymptomatic family members (Fig 1, A, I:1, I:2, and II:4) were found to be slightly decreased, whereas C1Inh, C4, and C1q levels were within normal ranges.Table 1Complement profile of the familyBiochemistry of complement profile (normal ranges)Examined individualsAge (y)C4 (15-50 mg/dL)C1INH (14-35 mg/dL)C1INH function (%)C1q (100-300 μg/mL)I:1∗Heterozygous.8028.31946371I:2∗Heterozygous.8036.11965176II:1†Homozygous.589.47632184II:3†Homozygous.537.023.8428186II:4∗Heterozygous.47341555147II:5†Homozygous.4510.1731191Abnormal values are shown in bold. Levels for II:1, II:3, and II:5 are pretreatment values.∗ Heterozygous.† Homozygous. Open table in a new tab Abnormal values are shown in bold. Levels for II:1, II:3, and II:5 are pretreatment values. After informed consent was obtained, genetic analysis was performed for all family members, except 2 brothers who refused to be investigated. One healthy volunteer joined our investigation as a control subject. A total of 8 coding and uncoding exons, including deep exon-intron boundaries of the C1INH gene, were investigated completely in the proband. Sequencing analyses revealed a novel homozygous c.−101A>G change in the promoter region where the CAAT box is located (Fig 1, B). Two of the symptomatic sisters were also homozygous whereas the other examined family members were heterozygous for the same mutation (Fig 1, B). The control subject had a normal homozygous genotype (Fig 1, B). Because this alteration prevents the consensus sequence for the binding of transcription factors, the consequences on gene expression were planned to be investigated by using the RT-PCR method. The RT-PCR protocol was designed on simultaneous amplification of partial portions of the complementary C1INH (cC1INH; exons 5-7) gene and a housekeeping gene, β-actin (exons 2-6), as an internal control to normalize the quantification of the C1INH mRNA level. cDNAs were gained by means of reverse transcribing the total RNA (Mini Blood RNA Isolation Kit; Qiagen, Hilden, Germany) isolated from 200-μL peripheral blood samples from the healthy control subject and family members (I:1, II:3, II:4, and I:2). At that time, the proband was already undergoing treatment for her attacks. The quantification of the C1INH mRNA levels was realized by normalizing the ratio for C1INH to the housekeeping gene β-actin of tested individuals to the healthy control subject. This calculation resulted in a reduced level of C1INH mRNA in the homozygous patient comparable with the degrees seen in heterozygous individuals and not a lesser degree, as expected (Fig 1, C). It was previously demonstrated by Pappalardo et al5Pappalardo E. Zingale L.C. Cicardi M. Increased expression of C1-inhibitor mRNA in patients with hereditary angioedema treated with Danazol.Immunol Lett. 2003; 86: 271-276Crossref PubMed Scopus (58) Google Scholar that increased expression of C1INH mRNA occurred in patients undergoing treatment with danazol. Supporting this finding, one could rationalize our results by stating that the mRNA level of our homozygous patient would have been lower than that of the heterozygous individuals in proportion to her previously poor C1Inh profile if her blood sample for RNA experimentation were taken before the initiation of her therapy. The proband's C4 and C1Inh levels were 10.5 mg/dL and 6.27 mg/dL, respectively, during treatment, which is comparable with those of the asymptomatic heterozygous individuals of the family. Affected members of this family displayed a concordant complement profile with HAE-I, whereas heterozygous individuals had mild decrease of C1Inh activities. This could not be classified as HAE-II because the decrease was not more than 50% of normal values, and C4 levels were within normal limits. Although the parents of our proband did not previously mention consanguinity, they originated from the same small village, ultimately sharing a common ancestor. To our knowledge, only one autosomal recessive case has been reported to date in a family with c.−103C>T mutation, affecting the promoter region of C1INH, as noted by Verpy et al.4Verpy E. Biasotto M. Brai M. Misiano G. Meo T. Tosi M. Exhaustive mutation scanning by fluorescence-assisted mismatch analysis discloses new genotype-phenotype correlations in angioedema.Am J Hum Genet. 1996; 59: 308-319PubMed Google Scholar More recently, another case with a homozygous mutation in the coding region of the C1INH gene was described by Blanch et al6Blanch A. Roche O. Urrutia I. Gamboa P. Fontán G. López-Trascasa M. First case of homozygous C1 inhibitor deficiency [published erratum appears in J Allergy Clin Immunol 2007;119:745].J Allergy Clin Immunol. 2006; 118: 1330-1335Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar with a unique activation and consumption profile of the classical complement activation pathway different from that commonly observed in patients with HAE but similar to that seen in patients with acquired angioedema. We propose that the homozygous occurrence of c.−101A>G in our patient is pathogenic, not only because it is the only change in the C1INH gene but also because its recessive mode segregates with the affected individuals in our family and also because C1INH mRNA levels in heterozygous carriers are reduced in parallel to their C1Inh profile. Furthermore, c.−101A>G was not identified in 136 ethnically matched control chromosomes analyzed based on differential band patterns in single-strand conformation polymorphism analysis, which excludes its state for being an infrequent polymorphism. All 3 homozygous patients of our family responded well to danazol. This matter reflects the genotype-phenotype relationship of the promoter site mutations, which generally do not influence the quality but rather the quantity of the encoded protein. Therefore unlike the previously reported patients carrying homozygous structural mutations in the coded region of the C1INH gene, who could not benefit from treatment with androgens because of the lack of a wild-type allele, patients with homozygous promoter region mutations can benefit from the treatment.6Blanch A. Roche O. Urrutia I. Gamboa P. Fontán G. López-Trascasa M. First case of homozygous C1 inhibitor deficiency [published erratum appears in J Allergy Clin Immunol 2007;119:745].J Allergy Clin Immunol. 2006; 118: 1330-1335Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar In conclusion, we describe here the second autosomal recessive family with a novel mutation affecting the C1INH promoter region (c.−101A>G). Identified sequence alteration in homozygous form causes moderate-to-severe life-threatening HAE symptoms; on the other hand, these symptoms respond well to attenuated androgens. We thank the family members who participated in this study. We also thank Duzen Laboratories, Istanbul, Turkey, for allowing us to use their DNA sequencer, ABI3130.

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.

Objective: Hypersensitivity reactions (HR) to paracetamol are reported less commonly compared to other nonsteroidal antiinflammatory (NSAI) drugs. The aim of this study was to determine the rate of HR to paracetamol and paracetamol-propyphenazone combination (P-P) drugs in patients with analgesic intolerance and to assess the possible relations between HR to these drugs and other NSAI drugs as well as atopic diseases.Materials and Methods: A total of 262 patients with history of HR to analgesics within the past year were studied. Detailed history of atopy was taken and reported reactions were classified. Skin prick and intradermal tests were applied to the patients with P-P drug sensitivity. Single-blinded oral provocation tests with paracetamol were carried out in patients with negative skin test results.Results: HR to aspirin were high in men and patients with asthma [p=0.03; OR=1.86 (95% CI 1.033.33), (p=0.03; OR=3.21 (95% CI 1.08-9.53), respectively]. The frequency of HR to paracetamol and P-P drugs was 12.7% and 10.8% respectively and the most commonly reported reaction was urticaria- angioedema. Skin tests were negative in 29 out of 30 subjects. All were found to be tolerant to paracetamol in challenge test. Frequency of self-reported HR to aspirin, metamizol and other NSAI drugs were high in patients reporting HR to paracetamol and P-P drugs (p< 0.001).Conclusion: In conclusion, hypersensitivity to aspirin and NSAI drugs need to be searched in patients with hypersensitivity to paracetamol. Paracetamol may be given as an alternative drug to the patients reporting HR to P-P drugs after negative skin testing and challenging.

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.