Derya Unal

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

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.

Management of Hypersensitivity Reactions to Proton Pump Inhibitors: A Retrospective Experience

Background: We previously reported perfect specificity and low sensitivity of skin tests in proton pump inhibitor (PPI)-induced immediate hypersensitivity reactions in a prospective multicenter study. Here, in a retrospective study, we aimed to further evaluate the diagnostic workup procedures and characteristics of the patients with suspected PPI hypersensitivity. Methods: This national multicenter study was conducted as a retrospective chart review of patients with a history of PPI-induced immediate hypersensitivity reaction. A total of 60 patients were included. Results of diagnostic workup procedures (standardized skin-prick, intradermal, and oral-provocation tests with PPIs) and the characteristics of the patients were analyzed. Results: Lansoprazole was the most commonly suspected drug with 41 patients (68.3%), followed by pantoprazole in 12 patients (20.0%), esomeprazole in 6 (10.0%), rabeprazole in 4 (6.7%), and omeprazole in 1 (1.7%). Anaphylaxis (40 patients, 66.7%) was the most common clinical presentation followed by urticaria (17 patients, 28.3%). Diagnostic skin tests with the culprit PPI were positive in 13/26 patients (50.0%). Diagnostic oral-provocation tests were negative in 6/8 patients; 5 of these 6 patients had skin test results with the culprit PPI, and all were negative. Ten patients had at least 1 cross-reactivity. Extensive cross-reactivity (between >2 PPIs) was detected in 4 patients. Conclusions: Lansoprazole was the most frequently implicated drug and anaphylaxis was the most frequent manifestation of PPI-induced hypersensitivity reactions. Physicians should be aware of the possible cross-reactivity among PPIs; however, a safe, alternative PPI can usually be detected by a thorough drug allergy workup.

Oral nickel exposure may induce Type I hypersensitivity reaction in nickel-sensitized subjects.

BACKGROUND Little is known about the clinical and immunological changes in the nickel allergic patients with systemic symptoms. We aimed to evaluate T helper cell responses of patients with different clinical presentations due to nickel. METHODS Patients having various allergic symptoms and positive patch test results to nickel and 20 controls underwent skin prick tests with nickel. IL-10, IL-4, IL-5 and IFN-gamma were measured in the culture supernatants of PBMC stimulated by nickel during lymphocyte proliferation test (LTT). RESULTS 69 patients (56 female, mean age: 49.2 ± 13.1), 97% having nickel containing dental devices and 20 controls (8 female, mean age 34.9 ± 12.06) were evaluated. Skin prick tests with nickel were positive in 70% of the patients (p<0.001), being significantly higher in the patients with urticaria/angioedema (p=0.02). The LTT stimulation index (p<0.0001), IL-4 (p=0.002), IFN-gamma (p=0.01), IL-5 (p=0.04) and IL-10 (p=0.003) were higher in the patient group. LTT stimulation index, IL-4 and IL-10 were significantly elevated in patients having urticaria, angioedema and respiratory symptoms when compared to those who had only oral symptoms or systemic dermatitis (p=0.004, p=0.002 and p=0.01, respectively). CONCLUSION This study suggests the presence of Type I hypersensitivity in addition to a Type IV immune reaction in patients with chronic systemic symptoms related to nickel. Nickel containing dental alloys and oral nickel intake seem to trigger systemic symptoms in previously nickel sensitized patients.

Usefulness of In Vivo and In Vitro Diagnostic Tests in the Diagnosis of Hypersensitivity Reactions to Quinolones and in the Evaluation of Cross-Reactivity: A Comprehensive Study Including the Latest Quinolone Gemifloxacin

Purpose Reports evaluating diagnosis and cross reactivity of quinolone hypersensitivity have revealed contradictory results. Furthermore, there are no reports investigating the cross-reactivity between gemifloxacin (GFX) and the others. We aimed to detect the usefulness of diagnostic tests of hypersensitivity reactions to quinolones and to evaluate the cross reactivity between different quinolones including the latest quinolone GFX. Methods We studied 54 patients (mean age 42.31±10.39 years; 47 female) with 57 hypersensitivity reactions due to different quinolones and 10 nonatopic quinolone tolerable control subjects. A detailed clinical history, skin test (ST), and single-blind placebo-controlled drug provocation test (SBPCDPT), as well as basophil activation test (BAT) and lymphocyte transformation test (LTT) were performed with the culprit and alternative quinolones including ciprofloxacin (CFX), moxifloxacin (MFX), levofloxacin (LFX), ofloxacin (OFX), and GFX. Results The majority (75.9%) of the patients reported immediate type reactions to various quinolones. The most common culprit drug was CFX (52.6%) and the most common reaction type was urticaria (26.3%). A quarter of the patients (24.1%) reacted to SBPCDPTs, although their STs were negative; while false ST positivity was 3.5% and ST/SBPCDPTs concordance was only 1.8%. Both BAT and LTT were not found useful in quinolone hypersensitivity. Cross-reactivity was primarily observed between LFX and OFX (50.0%), whereas it was the least between MFX and the others, and in GFX hypersensitive patients the degree of cross-reactivity to the other quinolones was 16.7%. Conclusions These results suggest that STs, BAT, and LTT are not supportive in the diagnosis of a hypersensitivity reaction to quinolone as well as in the prediction of cross-reactivity. Drug provocation tests (DPTs) are necessary to identify both culprit and alternative quinolones.

ASA must be given to classify multiple NSAID-hypersensitivity patients as selective or cross-intolerant.

The recently published article by Demir et al. (1) in Allergy included a large series of patients with a history of hypersensitivity reactions to NSAIDs which were confirmed by ASA or diclofenac challenge and classified according to the guidelines proposed by ENDA (2). Although cross-intolerance occurred in 50% of the patients, the most common reaction was single-NSAID-induced urticaria/angioedema or anaphylaxis (SNIUAA). Within this group, metamizol was the most frequent culprit drug (1). Their allergy work up consisted of a single-blind placebo-controlled drug provocation test (SBPCDPT) with the culprit drug, and, after confirming hypersensitivity, challenge with ASA or diclofenac was carried out to confirm or to exclude cross-reactivity. Interestingly, diagnosis was confirmed by SBPCDPT with the culprit drug for 76% of patients. A number of patients experienced anaphylaxis with different NSAIDs, and others developed anaphylaxis with one drug and urticaria with another. One case had angiodema with paracetamol and ibuprofen but tolerated diclofenac, and another patient had anaphylaxis with paracetamol and urticaria with metamizol but tolerated ASA. In another three patients, anaphylaxis occurred with naproxen and paracetamol; diclofenac, paracetamol and propyphenazone; and paracetamol and metamizol, respectively. This indicates that for a number of patients deemed SNIUAA by the authors, one drug can induce a given clinical entity whereas another drug can induce a different entity. Because different NSAIDs were involved, these patients do not fit properly into the ENDA definition of SNIUAA, which is ‘immediate hypersensitivity reactions to a single NSAID or to several NSAIDs belonging to the same chemical group, manifesting as urticaria, angioedema and/or anaphylaxis’ (2), as was pointed out by the authors (1). However, the consensus document recommends that a challenge with ASA must always be given to verify tolerance before considering these patients as selective immediate responders (SNIUAA) (2). We would also highlight that anaphylactic reactions can be observed in cross-intolerant subjects (3). As the position paper of ENDA was published, we have proposed that further phenotyping should be made to define and classify more precisely patients who develop hypersensitivity reactions to NSAIDs that fall outside of this group (4). By analyzing our large set of clinical records including information from more than 4000 cases with NSAID hypersensitivity, we have found patients with anaphylaxis and urticaria and/or angioedema induced by two or more NSAIDs but with tolerance to ASA. So these reactions should be considered as immediate selective responses to different drugs with good tolerance to ASA. Some of these cases have different clinical entities with different NSAIDs, for example anaphylaxis with paracetamol and angiodema with ibuprofen. Another important characteristics of these cases are that those with skin test positive to pyrazolones become negative over time as reported, as occurs with betalactam antibiotics (5). The article by Demir et al. (1) is interesting and highlights the need for a more precise phenotyping of cases with NSAID hypersensitivity and for reviewing the position documents of the ENDA group. Even if ASA is not involved in the reaction, it should be administered to clarify whether it was induced by a selective response or due to cross-intolerance. In fact, several studies recommend that ASA is tested before the culprit drug (6). The possibility also exists, as in the case of the Demir study and other studies, that subjects can respond to ASA and other NSAIDs but tolerate other strong COX-1 inhibitors like indomethacin.

A Practical and Successful Desensitization Protocol for Immediate Hypersensitivity Reactions to Iron Salts

Orally administered iron salts (OAS) are widely used in the management of iron deficiency anemia and hypersensitivity reactions to OAS are not common. If an offending drug is the sole option or is significantly more effective than its alternatives, it can be readministered by desensitization. The oral desensitization protocols for iron published so far concern either desensitization that was completed only over a long period or did not attain the recommended therapeutic dose. We aimed to develop a more effective protocol. We report here on 2 patients who experienced hypersensitivity reactions to OAS. After confirming the diagnosis, both patients were desensitized to oral ferrous (II) glycine sulfate complex according to a 2-day desensitization protocol. A commercial suspension of oral ferrous glycine sulfate, which contains 4 mg of elemental iron in 1 ml, was preferred. We started with a dose as low as 0.1 ml from a 1/100 dilution (0.004 mg elemental iron) of the original suspension and reached the maximum effective dose in 2 days. Both patients were successfully desensitized and they went on to complete the 6-month iron treatment without any adverse effects. Although hypersensitvity reactions to iron are not common, there is no alternative for iron administration. Therefore, desensitization has to be the choice. This easy desensitization protocol seems to be a promising option. i 2014 S. Karger AG, Basel

An unusual dual hypersensitivity reaction to moxifloxacin in a patient

Both immediate and nonimmediate type hypersensitivity reactions (HRs) with a single dose of quinolone in the same patient have not been previously reported. A 47-year-old female patient referred to us because of the history of a nonimmediate type HR to radio contrast agent and immediate type HR to clarithromycin. She experienced anaphylaxis in minutes after the second dose of 50 mg when she was provocated with moxifloxacin. She was treated immediately with epinephrine, fluid replacement and methylprednisole and pheniramine. On the following day she came with macular eruptions, and she was treated with methylprednisolone. The positive patch test performed with moxifloxacin as well as the lymphocyte transformation test proved the T-cell mediated HR. In order to prove the immediate type HR, basophil activation test was performed but was found negative. This case report presents for the first time the 2 different types of HRs in a patient with a test dose of quinolone.

Evaluation of the left venticular systolic function with the measurement of global longitudinal strain by Speckle tracking echocardiography in anaphylaxis

Background It is not known how cardiac functions are affected during anaphylaxis. Objective Our aim was to measure the cardiac functions shortly after an anaphylaxis attack using a new technique that detects subclinical left ventricular dysfunction. Methods Patients in our hospital who experienced anaphylaxis and urticaria (control group) due to any cause were included in the study. Tryptase levels were measured on the third hour of the reaction and 6 weeks later. Left ventricular systolic functions were evaluated with global strain measurement using echocardiography, approximately 4 hours and 6-week post reaction. Results Twelve patients were included in the anaphylaxis group (83.3% female; mean age, 43.25 ± 9.9 years). The causes of anaphylaxis were drug ingestion (n = 11) and venom immunotherapy. Eight of the anaphylactic reactions (66.7%) were severe and in 9 reactions (75%) tryptase levels increased. In the anaphylaxis group, strain values measured shortly after anaphylaxis were significantly lower than those calculated 6 weeks later (p < 0.001) and tryptase levels significantly increased (p = 0.002). The strain values measured both shortly after anaphylaxis and 6 weeks later did not differ according to severity of anaphylaxis. In severe anaphylaxis, tryptase levels during anaphylaxis and 6 weeks later were significantly higher (p = 0.019, p = 0.035). The control group evidenced no differences regarding strain and tryptase levels measured at reaction and 6 weeks later. At reaction, in the anaphylaxis group, the tryptase levels were higher and the strain values were lower than those in the urticaria group (p = 0.007, p = 0.003). Conclusion Cardiac dysfunction may develop during an anaphylaxis independent of severity of reaction.

Bir Kalsiyum Kanal Blokeri Olan Lerkanidipin Kullanımı Sonrası Akut Ürtiker ve Anjiyoödem

Anjiyotensin dönüştürücü enzim (ACE) inhibitörleri, anjiyotensin reseptör blokerleri (ARB), beta-blokerler ve kalsiyum kanal blokerleri gibi çeşitli antihipertansif ilaçlar, allerjik reaksiyona neden olabilir. Kalsiyum kanal blokerlerine bağlı ürtiker ve anjiyoödem ise olgu sunumları halinde nadiren bildirilmektedir. Bu bildiride bir kalsiyum kanal blokeri olan lerkanidipin kullanımını takiben akut ürtiker ve anjiyoödem gelişen ilk olguyu sunmaktayız. ABSTRACT

Impact of high serum Immunoglobulin E levels on the risk of atherosclerosis in humans

Background Epidemiological studies show that immunoglobulin E (IgE) levels were higher in subjects with acute coronary events. However, it is unknown if the increased IgE level is a marker of future coronary incidents and whether it may be regarded as a risk factor of an ischemic heart disease. Objective Our aim was to investigate the relationship between IgE levels and some atherosclerotic markers in patients without known atherosclerotic disease. Methods Fifty patients (mean age, 40.96 ± 10.8 years) with high serum IgE levels due to various conditions who did not display evidence of an atherosclerotic disease and 30 healthy control subjects (mean age, 47 ± 8.27 years) were included in the study. Atherosclerotic disease markers including adhesion molecules like vascular cell adhesion molecule-1, intercellular adhesion molecule-1, proinflammatory cytokines such as interleukin-6, endothelin-1, and systemic inflammatory markers such as high sensitivity C-reactive protein were determined by enzyme-linked immunosorbent assay (ELISA). Endothelial functions of the coronary arteries were determined by coronary flow reserve (CFR) measurements and carotid intima media thickness using transthoracic Doppler echocardiography. Results CFR was significantly lower in the patient group when compared with the control group (p<0.001; 95% confidence interval, -0.79 to-0.20) while carotid media thicknesses were not different between 2 groups. There were no differences in ELISA test results between the 2 groups. Conclusion Our results showed that CFR as an early marker of endothelial dysfunction was significantly lower in patients with high IgE levels. This finding seems to support the role of IgE in the vascular pathology of atherosclerosis.