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.

Food allergy due to olive.

We report the case of a 28-year-old man who presented palatal itching and genaralized urticaria following ingestion of olive 3 years after being diagnosed with olive pollinosis. The patient did not have a history of food allergy or urticaria. The results of skin prick tests with aeroallergens including latex were positive for house dust mite and olive pollen. The results of prick tests and prick-to-prick tests for olive fruit were positive, as were those of specific immunoglobulin E tests to olive pollen and fruit. The results of prick tests to peach, pear, kiwi, melon, and nut were negative. Nasal provocation with olive pollen gave positive results. An open oral provocation test with olive oil did not cause symptoms. This case is unique in that the patient developed olive fruit allergy in the presence of olive pollinosis, and he did not experience allergic symptoms to fruits other than olive, thus enabling us to define a new pollen-food (olive-olive) syndrome.

Prevalence of cypress pollen sensitization and its clinical importance in Izmir, Turkey, with cypress allergy assessed by nasal provocation.

BACKGROUND AND OBJECTIVE: Pollens from the Cupressaceae family are considered important allergens in the Mediterranean area, though reports of the prevalence of allergic symptoms have ranged from 1.04% to 35.4%. Our aim was to detect the prevalence of cypress pollen sensitization and determine its clinical importance in patients with seasonal respiratory allergy. METHODS: We used skin prick tests (SPT) and serum specific IgE assays to reveal sensitization to cypress pollen. In patients who showed positive results to cypress pollen, a nasal provocation test (NPT) with pollen extract was used to assess the target organ response. RESULTS: Sixty-five (14.3%) of 455 patients showed positive SPT responses to Cupressus sempervirens extract. Only 1 patient was monosensitized while 64 patients were polysensitized. Among those, 2 pollen cosensitizations were found to be significant (86% were cosensitized to grasses and 72% were cosensitized to olive (P < .001). Serum specific IgE to cypress pollen was measured in 50 of the 65 patients; findings were positive for 37. When these 37 patients underwent NPT with C sempervirens allergen extract, only the single monosensitized patient had a positive NPT. CONCLUSION: A positive SPT to cypress pollen may not reflect the true prevalence of sensitization. We assume that in the absence of a positive NPT, positive SPT results might be related to the presence of cross-reactivity between pollen species.

New onset egg allergy in an adult.

We report newly presenting systemic and local allergic reactions to egg in a 55-year-old woman. The patient did not have a history of egg allergy in childhood or occupational exposure to egg proteins; nor did she report any disease that is known to be related to food allergy. A skin prick test with commercial extracts, prick-to-prick test, CAP radioallergosorbent assay, and a double-blind, placebo-controlled food challenge test were used to prove egg allergy. Because egg allergy mainly affects children and symptoms frequently disappear with age, the late onset in this patient is rare.

Eosinophil infiltration of the oesophageal mucosa in patients with pollen allergy during the season.

BACKGROUND: The oesophagus is normally devoid of eosinophils. There are some disorders accompanying with eosinophil infiltration. Food allergy has been reported as a common reason, especially in children but some other studies have also indicated that aeroallergens might have a role in oesophageal eosinophil accumulation. OBJECTIVE: In this study we investigated whether there is any eosinophil recruitment in the oesophagus of pollen-allergic patients who had respiratory symptoms during the season. METHODS: Thirty-eight symptomatic patients (allergic rhinitis (AR) with or without asthma) who had sensitization to grass pollen were included in the study during the pollen season. Controls were composed of 25 healthy non-atopics and 24 patients diagnosed as having gastro-oesophageal reflux disease. Reflux was excluded in allergic and non-atopic groups, whereas the presence of allergy was eliminated in control groups. Gastrointestinal endoscopy was performed in all participants, and biopsy specimens were taken from both the proximal and the distal oesophagus to evaluate eosinophil accumulation. At the same time, blood eosinophil numbers were counted. Results Oesophageal eosinophil accumulation was found in 10 allergic patients (26%) and in five patients (21%) with gastro-oesophageal reflux disease but none of the healthy controls had eosinophils (0%) (P<0.05). Blood eosinophils were higher in these 10 patients than the rest of the 28 patients without infiltration. In this group, blood eosinophils were also correlated with the number of accumulated eosinophils in the oesophagus (P<0.001). There was more intense eosinophil infiltration at the distal part of the oesophagus in the reflux group when compared with the allergic group (mean 7.6+/-5.6 vs. 3.2+/-3.7). Nevertheless, eosinophils were found to be concentrated (mean 5.5+/-7.3) in the proximal oesophagus of allergic patients, although it was 1.7+/-1.5 in reflux patients (P>0.05). Conclusion Our results showed that eosinophil infiltration might be observed in oesophageal tissue of patients with respiratory tract allergy during the symptomatic period. This finding may possibly reflect the systemic and common mucosal aspects of allergic inflammation.

Low B12 levels in chronic idiopathic urticaria.

Recent studies suggest that autoimmune mechanisms may be involved in the etiology of chronic idiopathic urticaria (CIU). There is a higher prevalence of B12 deficiency in autoimmune diseases and possibly in gastric Helicobacter pylori (H. pylori) infection. The frequency of B12 deficiency in CIU is unknown. Our objective in this study was to determine the prevalence of B12 deficiency in patients with CIU and also its relationship to gastric H. pylori infection and serologic markers of autoimmunity in these groups. Thirty-three patients with CIU and 27 healthy controls were included in the study. Serum vitamin B12 levels, H. pylori infection and serological markers of autoimmunity (anti-thyroglobulin, thyroid microsomal, gastric parietal cell and antinuclear autoantibodies) were investigated. H. pylori infection was determined according to serology and gastric biopsy in 19 patients, serology and urea breath test in 4 patients and serology alone in the remaining 10 patients. Serum B12 levels were below the normal reference range in 11/33 (33.3%) patients with CIU. The mean serum B12 levels among patients with CIU and the controls were 281+/-127.5 pg/ml and 465.1+/-140.3 pg/ml (p=0.0001), respectively. Anti-thyroid antibodies were positive in 6 of 11 patients (54.5%) with low B12 levels, but only in 4 of 27 (14.8%) healthy controls (p=0.019). Anti-GPC antibodies were positive in 4 of 11 (36.4%) patients with CIU and low B12 levels, but only in 2 of 27 (7.4%) healthy controls (p=0.047). In CIU patients, there was no difference in the frequency of IgG H. pylori antibodies between those with low B12 levels and normal B12 levels. Among the 19 patients who had been performed gastric endoscopy, 15 patients (78.9%) had chronic antral gastritis, 2 patients (10.5%) had atrophic gastritis and there were normal findings in 2 patients (10.5%). In conclusion, serum B12 levels were found to be below the normal reference range in 33% of the patients with CIU. An association between low B12 levels and H. pylori could not be shown. The higher frequency of antithyroid and anti-GPC antibodies in patients with low B12 levels suggest that low B12 levels in CIU may be autoimmune in nature.

Nerve growth factor or IL-3 induces more IL-13 production from basophils of allergic subjects than from basophils of nonallergic subjects.

BACKGROUND: Studies show that nerve growth factor (NGF) exhibits immunomodulatory activity. This neurotrophin is found at high levels in the serum of asthmatic individuals, is released during allergic reactions, and is reported to augment in vitro histamine and leukotriene C4 release by human basophils. OBJECTIVE: Because basophils represent a substantial source of IL-4 and IL-13, we tested the effects of NGF on the secretion of these cytokines by cells prepared from allergic subjects and cells prepared from nonallergic subjects. METHODS: Cytokine and histamine were measured in culture supernatants by ELISA and fluorimetry, respectively. Both real-time RT-PCR and conventional RT-PCR were used to measure IL-13 mRNA expression. NGF receptor expression was determined by 2-color flow cytometry. RESULTS: Basophil suspensions from allergic subjects secreted some 2.5-fold greater levels of IL-13 when cultured with NGF than did cells prepared from normal control subjects. Flow cytometry revealed no significant differences in TrkA receptors on basophils to explain these findings. The levels of IL-13 secreted by the 2 groups of donors also differed when cells were activated with IL-3 but not when they were activated with anti-IgE antibody. Both NGF and IL-3 failed to induce IL-13 in cell cultures depleted of basophils, suggesting that the measurable IL-13 was indeed basophil-derived. Real-time RT-PCR showed an average induction of IL-13 message above medium control that was 4.3 (+/- 1.7)-fold with NGF and 8.9 (+/- 3.7)-fold with IL-3. Finally, NGF priming resulted in a remarkable enhancement of IL-13 induced by anti-IgE. This was significantly greater than the priming observed for either the IL-4 or histamine when this stimulus was used. CONCLUSION: NGF (like IL-3) can both directly stimulate IL-13 secretion and modulate IgE-mediated responses in basophils. Its enhanced effect on cells from allergic individuals raises the importance of this cytokine in the pathogenesis of allergic disease.