Search Results (21)

Non-steroidal anti-inflammatory drugs (NSAIDs) can cause hypersensitivity reactions and lead to anaphylactic shock. These drugs also act as cofactors in allergic reactions. Lipid transfer proteins (LTPs), found in plants, represent a unique group of allergens in which cofactors play a crucial role. This case report describes a 26-year-old female who developed anaphylactic symptoms after ingesting grapes and taking ketoprofen. The patient experienced swelling of the lips, tongue, and throat, as well as shortness of breath, dizziness, and loss of consciousness, after consuming grapes and taking ketoprofen. She had previously used ketoprofen and acetylsalicylic acid without issues but had developed urticaria on several occasions after consuming multi-ingredient dishes. Skin prick tests showed positive results for peanut and orange allergens. Further testing using the ALEX multiparametric test detected antibodies to several LTP allergens. Intradermal tests with ketoprofen yielded a positive result, although irritant reactions could not be ruled out. A provocation test with acetylsalicylic acid (ASA) showed no adverse reactions. Skin tests with ibuprofen were negative, and provocation tests confirmed its tolerance. A diagnosis of LTP allergy and selective ketoprofen allergy was made, with the recommendation to avoid ketoprofen and follow a diet excluding foods from the LTP group. Full article

Background and Objectives: Early-type drug hypersensitivity reactions (DHRs) are observed within the first 1–6 h and most commonly manifest as urticaria and/or angioedema. Detailed anamnesis, skin prick tests (SPTs), intradermal tests (IDTs), and oral/intramuscular/intravenous drug provocation tests (DPTs) can be used to identify the drug responsible. We aimed to evaluate the demographic characteristics, responsible drugs, DHR types, and DPT results used in the diagnosis of drug allergy in patients who presented to our clinic with suspected drug allergies. Materials and Methods: The medical records of patients who presented with a suspicion of an early-type DHR between February 2019 and December 2024 were retrospectively evaluated through the hospital information management system. A total of 188 adults who underwent diagnostic drug testing were included. Results: The diagnosis of drug allergy was confirmed in 51 (27%) patients. In 137 (73%) patients, the diagnosis of drug allergy was excluded after DPTs. In 78 of the 188 patients, there was a DHR to a single suspected drug. The other 110 patients had DHR histories with multiple drugs. The rate of confirmation of a drug allergy from diagnostic tests was higher in those who described a history of multiple drug allergies. Amongst the antibiotics, beta-lactam antibiotics (n = 47) were the most frequently suspected drugs. The rate of positive DPTs (n = 4; 8%) was lower in patients with suspected beta-lactam allergies than other antibiotics (p = 0.002). NSAIDs (n = 60) were the second most common group of suspected drug allergies. With regard to IgE or COX-1-mediated mechanisms, there was no statistically significant difference in DPT positivity among these NSAIDs (p = 0.414). The severity of the initial early-type DHRs were grade 1 (n = 168; 80%), grade 2 (n = 14; 7%), and grade 3 (n = 14; 7%). If the patients had redness, itching, urticaria, angioedema, dyspnea, cyanosis, desaturation, syncope, tachycardia, or hypotension during their initial DHRs, the positive diagnostic drug test rate was statistically significantly higher. However, experiencing diarrhea, nausea, and vomiting were not found to be associated with positive diagnostic drug tests. Drug allergies were confirmed with SPTs or IDTs in all patients in whom adrenaline was used during initial reactions. Conclusions: Contrary to the prevailing notion that drugs (especially beta-lactams) are the predominant cause of allergic reactions, this study demonstrated that the actual prevalence of drug allergies is, in fact, low. Full article

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) exacerbated respiratory disease (N-ERD) is associated with chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, and NSAID hypersensitivity. An overproduction of leukotrienes characterizes the pathomechanism of the disease. N-ERD patients often report breathing difficulties after consuming alcohol. These symptoms have been observed in patients receiving either aspirin therapy after desensitization (ATAD), therapy with the biologics dupilumab (anti-IL-4Ra antibody) and omalizumab (anti-IgE antibody), or intranasal corticosteroid treatment (INCS). Methods: This retrospective, real-world study assessed the severity of alcohol-related and non-alcohol-related respiratory symptoms in CRSwNP/N-ERD patients 3–6 months after ATAD, biologic (dupilumab or omalizumab), or INCS therapy. A total of 171 patients (98 women and 73 men) were enrolled in the study. All groups received standard INCS therapy. Sixty-three patients were treated with ATAD; 48 received biologics (dupilumab n = 31; omalizumab n = 17); and 60 received INCS only and served as a control group. Alcohol-dependent symptoms and typical CRS symptoms (alcohol-independent) were quantified using visual analog scales (VAS). Results: ATAD and biological therapy significantly reduced VAS scores for alcohol dependence and CRS symptoms. In the control group receiving INCS, only non-alcohol dependent CRS symptoms improved significantly (p < 0.05). The most significant differences in pre/post scores were observed in patients receiving dupilumab, with the most significant improvement in alcohol-dependent and CRS symptoms (dupilumab > omalizumab > ATAD). Conclusions: This real-world study shows that alcohol-related respiratory symptoms are a relevant parameter in CRSwNP/N-ERD patients. Patients benefit more from biologic therapy than from ATAD in terms of their alcohol-related symptoms and other CRS symptoms. Future studies should include placebo-controlled oral alcohol challenge. Full article

Fixed drug eruption (FDE) is a well-recognized, non-immediate, drug hypersensitivity reaction, often attributed to the use of various medications, most commonly non-steroidal anti-inflammatory drugs (NSAIDs) and antibiotics. Cross-reactivity between related NSAIDs in FDE has been reported, but among chemically unrelated NSAIDs, is rare. Herein, we present a rare well-documented case where a patient initially displayed tolerance to etoricoxib after experiencing a nimesulide-induced FDE. Subsequently, the patient developed an etoricoxib-induced FDE, accompanied by the development of bullous lesions. This case report and the literature review on comparable FDE occurrences shed light on the intricate nature of FDEs, suggesting the possibility of cross-reactivity between chemically related and unrelated NSAIDs or the emergence of new drug-specific T cells without cross-reactivity after multiple exposures to a drug in a susceptible patient. Our case underscores the importance of increased awareness and vigilance among both physicians and patients in the realm of personalized medicine. Further research is needed to unravel the intricate mechanisms behind these drug eruptions, improve diagnostic approaches, and enhance patient care. Full article

Mastocytosis is a myeloproliferative neoplasm characterized by abnormal proliferation and activation of clonal mast cells typically bearing the KITD816V mutation. Symptoms manifest due to the release of bioactive mediators and the tissue infiltration by neoplastic mast cells. Mast cell activation symptoms include flushing, pruritus, urticaria, abdominal cramping, diarrhea, wheezing, neuropsychiatric symptoms, and anaphylaxis. Up to 50% of patients with mastocytosis report a history of provoked and unprovoked anaphylaxis, with Hymenoptera venom and drugs the most common culprits. NSAIDs, antibiotics, vaccines, perioperative medications, and radiocontrast media are often empirically avoided without evidence of reactions, depriving patients of needed medications and placing them at risk for unfavorable outcomes. The purpose of this review is to highlight the most common agents responsible for adverse drug reactions in patients with mastocytosis, with a review of current epidemiology, diagnosis, and management of drug hypersensitivity and Hymenoptera venom allergy. Full article

Background: Human leukocyte antigen (HLA) genes are important in many immune processes and contribute to many adverse drug reactions. Whether genetic variations in the HLA region are associated with non-steroid anti-inflammatory drug (NSAID) hypersensitivity remains uncertain. Therefore, the aim of our study was to identify HLA genetic variations in patients with NSAID hypersensitivity in the Taiwanese population. Methods: This hospital-based, retrospective case-control study enrolled 37,156 participants with NSAID exposure from the Taiwan Precision Medicine Initiative (TPMI), who were all genotyped and imputed to fine map HLA typing. Our study assigned 1217 cases to the NSAID allergy group and 12,170 controls to a matched group. Logistic regression analyses were utilized to explore associations between HLA alleles and NSAID hypersensitivity. Results: Overall, 13,387 patients were genotyped for eight major HLA alleles. Allele frequencies were different between the two groups. In the NSAID allergy group, the genotype frequencies of HLA-A*02:01, HLA-A*34:01, and HLA-DQA1*06:01 were found to be markedly elevated compared to the control group, a significance that persisted even after applying the Bonferroni correction. Furthermore, the risk of NSAID allergy demonstrated a significant association with HLA-A*02:01 (OR = 1.29, p < 0.001) and HLA-A*34:01 (OR = 9.90, p = 0.001), in comparison to their respective counterparts. Notably, the genotype frequency of HLA-B*46:01 exhibited a significant increase in the severe allergy group when compared with the mild allergy group. Conclusions: We identified HLA genotypes linked to the onset and severity of NSAID hypersensitivity. Our findings establish a basis for precision prescription in future clinical applications. Full article

Progressive articular surface degradation during arthritis causes ongoing pain and hyperalgesia that lead to the development of functional disability. TRPA1 channel significantly contributes to the activation of sensory neurons that initiate neurogenic inflammation and mediates pain signal transduction to the central nervous system. Peptide Ms 9a-1 from the sea anemone Metridium senile is a positive allosteric modulator of TRPA1 and shows significant anti-inflammatory and analgesic activity in different models of pain. We used a model of monosodium iodoacetate (MIA)-induced osteoarthritis to evaluate the anti-inflammatory properties of Ms 9a-1 in comparison with APHC3 (a polypeptide modulator of TRPV1 channel) and non-steroidal anti-inflammatory drugs (NSAIDs) such as meloxicam and ibuprofen. Administration of Ms 9a-1 (0.1 mg/kg, subcutaneously) significantly reversed joint swelling, disability, thermal and mechanical hypersensitivity, and grip strength impairment. The effect of Ms 9a-1 was equal to or better than that of reference drugs. Post-treatment histological analysis revealed that long-term administration of Ms9a-1 could reduce inflammatory changes in joints and prevent the progression of cartilage and bone destruction at the same level as meloxicam. Peptide Ms 9a-1 showed significant analgesic and anti-inflammatory effects in the model of MIA-induced OA, and therefore positive allosteric modulators could be considered for the alleviation of OA symptoms. Full article

Background: We aimed to assess the real-life prevalence, patient profile, and clinical presentation of drug hypersensitivity to NSAIDs in children after an incidence of an adverse event during treatment, verified by a drug challenge test. Methods: We included 56 children, aged 4–18 years, referred to our allergy clinic due to the incidence of adverse reaction during treatment. Skin prick tests and a drug provocation test were performed in all patients. Diagnostics for persistent urticaria were performed. Results: In 56 patients suspected of drug allergy, we proved NSAID hypersensitivity in 17 patients (30.1%). In 84.9% (n = 47) of patients, the clinical manifestations of hypersensitivity revealed angioedema and urticaria. The most common culprit drug among NSAIDs in children was ibuprofen. Thirty-one (55.4%) reactions were immediate, and 25 (44.6%) were delayed or late. Previous history of allergy was a risk factor for NSAID hypersensitivity (p = 0.001). Vitamin D deficiency in the blood serum was a risk factor for NASID hypersensitivity (OR = 5.76 (95% Cl: 1.42–23.41)). Conclusions: Hypersensitivity to NSAIDs is a difficult diagnostic problem in pediatric allergy. The most common manifestation of hypersensitivity to ibuprofen in children is acute urticaria and angioedema. Two important problems in the differential diagnosis are cofactors such as vitamin D levels and viral infections, which require further research. Full article

Drug hypersensitivity reactions (DHRs) are a type of adverse drug reactions with heterogeneous pathophysiological mechanisms and a broad spectrum of clinical manifestations. Since over-diagnosing is common in children, a complete allergy work-up is needed. A cross-sectional study was conducted at a tertiary care institution, covering the five-year period. Five hundred and four patients of both sexes, mean age 7.5 and with a medical history suggestive of DHR were evaluated. ENDA/EAACI guidelines were used for a diagnostic algorithm. Single drug hypersensitivity was registered in 375 patients and multiple drug hypersensitivity in 129. The main culprits in medical history were antibiotics (83%), non-steroidal anti-inflammatory drugs (NSAIDs) (8.4%) and analgoantipyretics (3.8%). Skin involvement was registered in 96.2%. DHRs were confirmed in 4.4% patients—six patients had positive skin tests and 13 had a positive drug provocation test. In the proven DHRs group, the main agents were antibiotics (72.7%), followed by NSAIDs (8.3%), and of all the skin manifestations, urticaria was most common (78.2%), followed by exanthema (10.5%) and angioedema (5.3%). Considering the above, anticipating DHRs and a proper referral of children to an allergologist is a key step in the assessment of drug hypersensitivity. A complete allergy work-up prevents unnecessary drug exclusion and allows most children to safely continue the use of first-line medications when needed. Full article

Oral drug provocation tests (DPT) are the basic diagnostic tool for the detection of hypersensitivity to non-opioid analgesics and for selecting a safe alternative for a patient. They are of great practical importance due to their common use, but the data on the follow-up of patients after negative DPT are still very scarce. We examined the further fate of 164 such adult patients after negative NSAID or paracetamol tests and analyzed which excipients in the studied drugs they could be exposed to after the diagnostic workup. A structured medical interview was performed 32.9 months (mean) after the provocation tests. Of the 164 patients, 131 (79.9%) retook the tested drug and 12 developed another hypersensitivity reaction, giving the estimated negative predictive value of 90.8%. These reactions were induced by acetylsalicylic acid, paracetamol, meloxicam, and diclofenac, and were clinically similar to the initial ones (most commonly urticaria and angioedema). There are 93 generics of these drugs on the local market, containing a total of 33 excipients for which hypersensitivity reactions have been reported. All available generics contain such excipients. Thirty-one patients (20.1%) did not take the previously tested drug again, most often because it was not needed or because they were afraid of another reaction. DPT with analgesics has a high diagnostic performance. A minority of patients had relapsed after reexposure. One of the underestimated reasons for this may be drug excipients provoking a reaction, so it is advisable to use exactly the same medical product that has been negatively tested. Many patients avoid reexposure to a given drug, despite negative tests, therefore very reliable patient education in connection with DPT is highly needed. Full article

Neuropathic pain is a condition that impacts a substantial portion of the population and is expected to affect a larger percentage in the future. This type of pain is poorly managed by current therapies, including opioids and NSAIDS, and novel approaches are needed. We used a cisplatin-induced model of neuropathic pain in mice to assess the effects of the cannabinoids THC and CBD alone or in varying ratios as anti-nociceptive agents. In addition to testing pure compounds, we also tested extracts containing high THC or CBD at the same ratios. We found that pure CBD had little impact on mechanical hypersensitivity, whereas THC reduced mechanical hypersensitivity in both male and female mice (as has been reported in the literature). Interestingly, we found that high CBD cannabis extract, at the same CBD dose as pure CBD, was able to reduce mechanical hypersensitivity, although not to the same level as high THC extract. These data suggest that, at least for CBD-dominant cannabis extracts, there is an increase in the anti-nociceptive activity that may be attributed to other constitutes of the plant. We also found that high THC extract or pure THC is the most efficacious treatment for reducing neuropathic pain in this model. Full article

Mastocytosis, a heterogeneous mastcell disease, include three different entities: cutaneous mastocytosis, systemic mastocytosis (SM) and mast-cell sarcoma. Tryptase levels can differentiate cutaneous mastocytosis from SM. In mastocytosis, quick onset drug hypersensitivity reactions (DHRs) that are facilitated by mastcell mediators, are investigated in adults. Due to the limited number of children with mastcell disease and increased serum tryptase levels, the role of drugs in this age group is less studied. In this review, we critically assessed relevant papers related with immediate DHRs in children with mastocytosis and discuss practical issues of the management. In childhood mastocytosis, anaphylaxis is frequently idiopathic, and elevated level of basal tryptase, and high burden of disease may increase the risk. Among drugs, antibiotics, NSAIDs and opioids can potentially induce anaphylaxis, anyway avoidance should be recommended only in case of previous reactions. Moreover, vaccinations are not contraindicated in patients with mastocytosis. The risk of severe systemic reactions after drugs intake seems to be extremely low and in general lower in children than in adults. Anyway, studies on this topic especially focusing on children, are missing to state final recommendations. Full article

Background: The role of genetics in non-steroidal anti-inflammatory drugs (NSAID) exacerbated respiratory disease (NERD) is unclear, with different candidates involved, such as HLA genes, genes related to leukotriene synthesis, and cytokine genes. This study aimed to determine possible associations between 22 polymorphisms in 13 cytokine genes. Methods: We included 195 patients (85 with NERD and 110 with respiratory disease who tolerate NSAIDs) and 156 controls (non-atopic individuals without a history of asthma, nasal polyposis (NP), or NSAID hypersensitivity). Genotyping was performed by sequence-specific primer polymerase chain reaction (PCR-SSP). Amplicons were analyzed by horizontal gel electrophoresis in 2% agarose. Results: Significant differences in allele and genotype frequency distributions were found in TNF (rs1800629), IL4 (rs2243248 and rs2243250), and IL10 (rs1800896, rs1800871, and rs1800872) genes in patients with NSAID hypersensitivity. In all cases, the minor allele and the heterozygous genotype were more prevalent in NERD. An association of TNF rs1800629 SNP with respiratory disease in NSAID-tolerant patients was also found. Conclusions: Retrospectively recorded, we found strong associations of NERD with polymorphisms in IL4, IL10, and TNF genes, suggesting that these genes could be involved in the inflammatory mechanisms underlying NERD. Full article

Salicylic acid and its derivatives (including acetylsalicylic acid/aspirin) are popular in medicine. They also occur naturally in many food products. The aim of the study was to investigate the effect of the personalized low salicylate diet (PLSD) on the reduction of asthma, rhinosinusitis and urticaria symptoms in patients with hypersensitivity to aspirin (ASA) or nonsteroidal anti-inflammatory drugs (NSAIDs). To achieve the research goal, a prospective, nonrandomized, baseline-controlled intervention study was conducted. Thirty patients diagnosed with NSAIDs hypersensitivity, who despite pharmacotherapy had symptoms of hypersensitivity, were included in the study. The PLSD was recommended for all participants for a period of two to four weeks. The intensity of subjectively declared symptoms of asthma, rhinosinusitis and urticaria were measured before and after dietary intervention, using, respectively, the asthma control test (ACT), the sino-nasal outcome test (SNOT-22) and the four-item itch questionnaire (FIIQ). Diet adherence and salicylate intake were measured by a 3-day food record. The severity of symptoms improved significantly after the intervention. The median of the ACT score was 24 scores before and 25 after the dietary intervention (p < 0.002), the median of the SNOT-22 score was 25 before and 13 after a dietary intervention (p < 0.0002) and the median of the FIIQ score was 5 before and 0 after a dietary intervention (p < 0.0002). The intake of salicylates decreased from 0.79 mg/day (before intervention) to 0.15 mg/day (p < 0.001) (during intervention). Although the usefulness of a low salicylate diet in the treatment of salicylate hypersensitivity is controversial, the results of our study indicate that the PLSD may have a positive effect in reducing symptoms of salicylate hypersensitivity and could be an additional tool supporting the therapy of these patients. Full article

Arthritis is a widespread inflammatory disease associated with progressive articular surface degradation, ongoing pain, and hyperalgesia causing the development of functional limitations and disability. TRPV1 channel is one of the high-potential targets for the treatment of inflammatory diseases. Polypeptide APHC3 from sea anemone Heteractis crispa is a mode-selective TRPV1 antagonist that causes mild hypothermia and shows significant anti-inflammatory and analgesic activity in different models of pain. We evaluated the anti-inflammatory properties of APHC3 in models of monosodium iodoacetate (MIA)-induced osteoarthritis and complete Freund’s adjuvant (CFA)-induced rheumatoid monoarthritis in comparison with commonly used non-steroidal anti-inflammatory drugs (NSAIDs) such as diclofenac, ibuprofen, and meloxicam. Subcutaneous administration of APHC3 (0.1 mg/kg) significantly reversed joint swelling, disability, grip strength impairment, and thermal and mechanical hypersensitivity. The effect of APHC3 was equal to or better than that of reference NSAIDs. Protracted treatment with APHC3 decreased IL-1b concentration in synovial fluid, reduced inflammatory changes in joints, and prevented the progression of cartilage degradation. Therefore, polypeptide APHC3 has the potential to be an analgesic and anti-inflammatory substance for the alleviation of arthritis symptoms. Full article