Obesity markers in patients with drug allergy and body fat as a predictor.

BACKGROUND: Obesity is a chronic low-grade inflammation state associated with several diseases. OBJECTIVE: To investigate a potential link between drug allergy and obesity, exploring whether the association depends on the type (immediate vs nonimmediate) or the severity of the reaction. METHODS: Anthropometric measurements, bioimpedance, and biochemical analysis, including serum adipokines, were performed in 90 consecutive adult patients studied for suspected drug allergy. Logistic regression models were developed to identify predictors of drug allergy. RESULTS: A total of 84 patients completed the diagnostic workup (78.6% women; mean age 39.58 ± 13.3 years). Drug allergy was confirmed in 39 patients and excluded in 45 (controls). Regarding body mass index, 42.2% had normal weight and 55.3% were overweight/obese. A total of 58% of women and 41% of men fulfilled the criteria for central obesity. Patients with drug allergy exhibited considerably higher body mass index, waist and hip circumferences, waist-hip ratio, fat mass, body fat percentage (BFP), trunk fat mass, leptin levels, and leptin-adiponectin ratio than controls. Similar results were obtained in the subgroup with immediate reactions, compared with the nonimmediate or unknown reactions. The higher the BFP and the number of reactions, the greater the odds of drug allergy (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.01-1.14 and OR, 2.82; 95% CI, 1.31-6.10, respectively). An immediate reaction was also a predictor of drug allergy (OR, 3.81; 95% CI, 1.30-11.14, P = .02), compared with nonimmediate or unknown reactions. In patients with drug allergy, BFP was a predictor of having an immediate reaction (OR, 1.12; 95% CI, 1.02-1.24, P = .02). CONCLUSION: Our study illustrates, for the first time, evidence of a link between obesity and drug allergy, particularly immediate reactions. The BFP emerged as a potential predictor of drug allergy.

Desensitization to antibiotics in children.

Drug hypersensitivity reactions can occur to almost all drugs and antibiotics are among the most common cause for this kind of reactions. Drug hypersensitivity may affect any organ or system, and manifestations range widely in clinical severity from mild pruritus to anaphylaxis. In most cases, the suspected drug is avoided in the future. In case of infection, there is usually a safe antibiotic alternative. Nonetheless, in some cases, no alternative treatment exists for optimal therapy. Under these circumstances, desensitization may be performed. Drug desensitization is defined as the induction of a temporary state of tolerance to a drug which can only be maintained by continuous administration of the medication responsible for the hypersensitivity reaction. Desensitization is mainly performed in IgE-mediated reactions. Increasing doses of the implicated drug are administered over a short period of time, until the therapeutic dose is achieved and tolerated. Very few studies confined to children are found in literature. Most of them are case reports. In general, the proposed desensitization schemes are similar to those used in adults differing only in the final dose administered. The purpose of this study is to review desensitization to antibiotics in children presenting and discussing three clinical practical cases of desensitization in this age group.

An experimental biological test to diagnose hypersensitivity reactions to carboplatin: new horizons for an old problem.

Carboplatin, a second-generation platinum compound, is a chemotherapeutic drug effective in many types of cancers. Its use is limited by the development of systemic allergic reactions in up to 30% of the cancer patients. Therefore, it is very important to make a correct diagnosis of true carboplatin allergy, for the crucial clinical implications. In this regard, no biological test is actually available to detect specific immunoglobulin E in the sera of patients allergic to carboplatin. We evaluated a new experimental biological test in patients with suspected immunoglobulin E-mediated reactions to carboplatin. Three patients with suspected hypersensitivity reactions to carboplatin underwent skin tests with an undiluted aliquot (10 mg/ml) of carboplatin preparation planned for infusion. Total serum immunoglobulin E and specific immunoglobulin E to the two platinum salts carboplatin and cisplatin were determined with the ImmunoCAP system (Phadia AB, Uppsala, Sweden). We detected specific immunoglobulin E to carboplatin in all three patients, whereas specific immunoglobulin E to cisplatin was observed in one patient. The positivity of specific immunoglobulin E against carboplatin in these three patients is a new and encouraging observation for the development of a new important instrument that can help clinicians in their therapeutic decisions, after a hypersensitivity reaction to a platinum salt.

Dietary parameters in patients with drug allergy: Assessing dietary inflammatory index.

BACKGROUND: Research on the increasing incidence of allergic diseases evidenced the role of diet as a potential key factor. Diet can modulate the low-grade systemic inflammation related to obesity and several diseases. There are no published data on drug allergy. AIM: To investigate a potential association between diet, including dietary inflammatory index (DII), and drug allergy. Also, to evaluate correlations between diet and obesity, inflammatory and metabolic parameters in patients with drug allergy. METHODS: Ninety consecutive patients studied for suspected drug allergy were evaluated in terms of dietary parameters, anthropometric measurements, bioimpedance and biochemical analysis. DII was calculated based on information collected from a food frequency questionnaire. RESULTS: After diagnostic work-up, 39 patients had confirmed drug allergy and 45 excluded, representing the study group and the control group, respectively. The majority (79%) were female, with mean age of 39.58±13.3 years. The 84 subjects revealed an anti-inflammatory diet pattern. No significative difference was found in DII scores between drug allergic patients and controls (-3.37±0.95 vs -3.39±0.86, p = 0.985). However, the patients with drug allergy revealed higher obesity and inflammatory parameters. A significative negative correlation was found between DII and adiponectin levels, in the control group (r = -0.311, p = 0.040). In the patient group, a significative positive correlation was observed between DII and triglycerides (r = 0.359, p = 0.032). No other correlations were found between DII and the assessed parameters. Patients with drug allergy presented a significative higher intake of mono-unsaturated fatty-acids comparing to controls (19.8±3.7 vs 17.8 ± 4.0, p = 0.021). No other statistically significant differences were achieved in dietary parameters, between patients and controls. CONCLUSION: The population assessed in this study revealed an anti-inflammatory diet profile. Although we have found in a previous work that the same patients with drug allergy revealed higher obesity and inflammatory parameters, the DII did not allow to distinguish between patients with drug allergy or controls. The DII scores correlated with triglycerides levels in the drug allergy patients and inversely with adiponectin levels in the control group. Larger studies are needed to clarify the potential role of the diet in drug allergy and its outcomes.

Psychological profiles of patients with suspected drug allergy.

BACKGROUND: Several studies demonstrate an important association between allergic diseases and patients' psychological characteristics. OBJECTIVE: To evaluate any differences in the psychological characteristics of patients studied for suspected drug allergy in comparison with healthy controls. A secondary aim was to assess differences between patients with confirmed versus excluded drug allergy, with respect to the clinical aspects. METHODS: The psychological characteristics of 115 consecutive patients >16 years-old, studied for suspected drug allergy were assessed. They were compared with healthy controls. Four validated questionnaires were used to evaluate anxiety, depression, alexithymia, and personality type. RESULTS: Eighty-eight patients completed the evaluation: 34 had confirmed drug allergy and 33 excluded. Forty-eight healthy subjects filled the 4 questionnaires. Increased neuroticism was associated with increased odds of belonging to the excluded drug allergy group (odds ratio [OR], 1.374; 95% confidence interval [CI], 1.173-1.609). Increased neuroticism (OR, 1.244; 95% CI, 1.065-1.453) and increased anxiety (OR, 1.210; 95% CI, 1.084-1.351) were associated with increased odds of confirmed drug allergy. However, higher extraversion decreased this likelihood (OR, 0.755; 95% CI, 0.643-0.888). The odds of having confirmed drug allergy was reduced by 79.7% (OR, 0.203; 95% CI, 0.060-0.694) for patients with 2 suspected drugs and by 84.6% (OR, 0.154; 95% CI, 0.029-0.809) for those with ≥3 in comparison to those with only one. Patients with moderate to severe reactions were more likely to have confirmed drug allergy (OR, 4.295; 95% CI, 1.105-16.693) than those with milder manifestations. CONCLUSION: Our results highlight that patients with drug allergy have a distinctive psychological profile. Psychological assessment may help to identify patients that would benefit from a targeted intervention.

Overview of Drug Allergy: From Immunogenetic Basis to Practice.

Drug therapy is often a balance between the beneficial and harmful effects of drugs. Drug allergic reactions are adverse reactions mediated by immunological mechanisms and usually not related to the pharmacological actions of the drug. They can be classified based either on the clinical presentation or the underlying immunological mechanism. Although uncommon, drug allergic reactions are unpredictable and can be very severe, even life threatening. The aim of this review was to provide clinicians from different medical specialties with a working tool to improve management of their patients with suspected drug allergy. It was conducted as a nonsystematic review, and attempts to describe the complexity of drug allergy. The information included ranges from pathophysiology to the heterogeneous clinical presentation, with a special focus on the drugs most frequently involved, as well as a classification of reactions and risk factors. Despite all advances in this challenging and complex field of allergy and clinical immunology, drug allergy is not yet fully established and understood. An exceptional contribution was brought by pharmacogenomics, even though a specific pharmacogenetic association has only been defined for a very limited number of drugs. Further studies are needed to obtain clearer answers when managing each individual case of drug allergy.

A terapêutica farmacológica consiste, frequentemente, num equilíbrio entre os efeitos benéficos e prejudiciais dos fármacos. As reações alérgicas a fármacos são reações adversas mediadas por mecanismos imunológicos e não relacionadas com as ações farmacológicas do fármaco. Podem ser classificadas quer com base na apresentação clínica, quer no mecanismo imunológico subjacente. Embora pouco comuns, as reações alérgicas a fármacos são imprevisíveis, podendo ser graves e potencialmente fatais. O objetivo da presente revisão da literatura foi disponibilizar aos clínicos de diversas áreas médicas uma ferramenta de trabalho para uma melhor abordagem dos seus doentes com suspeita de alergia a fármacos. Foi conduzida de forma não sistemática e procura descrever a complexidade das reações alérgicas a fármacos, desde a fisiopatologia à heterogeneidade da apresentação clínica. Foi dado especial destaque aos fármacos mais frequentemente envolvidos, à classificação das reações e aos fatores de risco. Apesar de todos os avanços nesta área desafiante e complexa da alergologia e imunologia clínica, a alergia a fármacos não está ainda completamente compreendida e estabelecida. A farmacogenética trouxe um contributo excecional, embora apenas para um número muito limitado de fármacos esteja definida uma associação farmacogenética. São necessários estudos adicionais que permitam obter respostas mais diretas na abordagem de cada caso individual de alergia a fármacos.

Reactions to cytostatic agents in children.

PURPOSE OF REVIEW: The current review will focus on drug hypersensitivity reactions to chemotherapy specifically to those drugs most used in children. We know that potentially all chemotherapeutic agents can cause infusion reactions, generally defined as adverse drug reactions. Of these, some are Type A, defined as expected and described in the characteristics of the drug and others, and Type B, defined as unexpected reactions which cannot be explained by the known toxicity profile of the drug. When an unexpected reaction occurs, drugs we can refer as hypersensitivity reactions (HSRs). Some of these (HSRs) are allergic reactions as they have an underlying immunologic mechanism. In general, the cytotoxic agents most commonly associated with HSRs are the platinum salts derivatives, taxanes, pegylated liposomal doxorubicin, L-asparaginase, procarbazine, etoposide, bleomycin, and cytarabin. RECENT FINDINGS: HSRs may also occur in children with cancer, during the treatment with chemotherapeutic drugs. The most used drugs of this group in children to cause HSRs are: carboplatin, L-asparaginase, and methothrexate. The aim of this review is to summarize the incidence and the clinical features of HSRs occurring with these drugs in children. SUMMARY: The aim of this review is to summarize the incidence and the clinical features of HSRs occurring with these drugs in children. The current review will focus on the most involved drugs in children, the type of reactions, the mechanisms involved, and the best way to manage them.

Intradermal Tests for Diagnosis of Drug Allergy are not Affected by a Topical Anesthetic Patch.

The use of topical anesthesia to perform intradermal tests (IDTs) for drug allergy diagnosis was never investigated. We aimed to determine the effects of a topical anesthetic patch containing prilocaine-lidocaine on wheal size of IDT with drugs. Patients who had positive IDT as part of their investigation process of suspected drug hypersensitivity were selected. IDT were performed according to guidelines. Anesthetic patch (AP) was placed and the same prior positive IDT, as well as positive histamine skin prick test (SPT) and negative (saline IDT) controls, were performed in the anesthetized area. Patients with negative IDT were also included to check for false positives with AP. Increase in wheals after 20 minutes both with and without AP was recorded and compared. 45 IDT were performed (36 patients), of which 37 have been previously positive (14 antibiotics, 10 general anesthetics, 6 non-steroidal anti-inflammatory drugs, 3 iodinated contrasts, 3 anti-Hi-histamines and 1 ranitidine). Mean histamine SPT size without the AP was 4.7 mm [95%CI (4.4-5.1]), and 4.6 mm [95%CI(4.2-5.0)] with anesthesia. Mean wheal increase in IDT for drugs without the anesthesia was 4.5 mm [95%CI(3.3-5.7)] and with anesthesia was 4.3 mm [95%CI(2.8-5.8)]. No statistical significant differences were observed between skin tests with or without AP for histamine SPT (P=0.089), IDT with saline (P=0.750), and IDT with drugs (P=0.995). None of the patients with negative IDT showed positivity with the AP, or vice-versa. The use of an AP containing prilocaine-lidocaine does not interfere with IDT to diagnose drug allergy, and no false positive tests were found.