Health-related quality of life in severe hypersensitivity reactions: focus on severe allergic asthma and hymenoptera venom anaphylaxis-a cross-sectional study.

Background: Growing evidence reveals the important role of clinical psychological factors in chronic-immune diseases. The aim of this study was to investigate Health-Related Quality of Life (HR-QoL), depression, anxiety, and alexithymia in patients with severe hypersensitivity reactions such as Severe Allergic Asthma (SAA) and Hymenoptera Venom Anaphylaxis (HVA). Methods: The Short-Form Health Survey-36 (SF-36), the Beck Depression Inventory Questionnaire (BDI-II), the Hamilton Anxiety Rating Scale (HAM-A) and the Toronto Alexithymia Scale (TAS-20) were used to assess HR-QoL and clinical psychological features of patients with SAA and HVA. Results: Overall, 78 patients were recruited. Patients with SAA (n = 35) reported lower scores for physical functioning [65 (58-75) vs. 90 (85-95); p = <0.001], role limitations due to physical health [25 (0-50) vs. 62 (50-75); p = 0.004], bodily pain [47.5 (41.1-61.3) vs. 55.5 (55-96); p = 0.001], general health [40 (30-60) vs. 70 (50-80); p = 0.0003] and social functioning [50 (37.5-62.5) vs. 62.5 (54.9-75); p = 0.007] while higher scores for depressive symptoms [14 (11-15.4) vs. (9.5 (6-15.4); p = 0.05)] compared to HVA patients (n = 43). All the dimensions of SF-36 were negatively correlated with anxiety (r from -0.26 to -0.66; p all < 0.01) and depressive symptoms (r from -0.44 to -0.73; p all < 0.001). Alexithymia was negatively correlated with vitality (r = -0.28; p = 0.02) and mental health (r = -027; p = 0.03). Additionally, patients with alexithymia (38% of participants) showed higher levels of depressive symptoms [9.5 (10-19) vs. 14 (6-13.9); p = 0.005] and anxiety levels [31 (27.9-35) vs. 24 (16-33.9); p = 0.02]; they also showed less vitality [40 (39.9-50) vs. 55 (50-60) p = 0.01], social functioning [50 (37.5-62.5) vs. 62.5 (50 vs. 75); p = 0.01] and mental health [48 (44-60) vs. 68 (56-76); p = 0.004]. Conclusion: Clinical psychological features due to severe hypersensitive reactions may contribute to the patient's perceived HR-QoL. Focused clinical psychological interventions should be promoted to improve the clinical management of such conditions.

Use of intravenous iron and risk of anaphylaxis: A multinational observational post-authorisation safety study in Europe.

PURPOSE: This post-authorisation safety study estimated the risk of anaphylaxis in patients receiving intravenous (IV) iron in Europe, with interest in iron dextran and iron non-dextrans. Studies conducted in the United States have reported risk of anaphylaxis to IV iron ranging from 2.0 to 6.8 per 10 000 first treatments. METHODS: Cohort study of IV iron new users, captured mostly through pharmacy ambulatory dispensing, from populations covered by health and administrative data sources in five European countries from 1999 to 2017. Anaphylaxis events were identified through an algorithm that used parenteral penicillin as a positive control. RESULTS: A total of 304 210 patients with a first IV iron treatment (6367 iron dextran), among whom 13-16 anaphylaxis cases were identified and reported as a range to comply with data protection regulations. The pooled unadjusted incidence proportion (IP) ranged from 0.4 (95% confidence interval [CI], 0.2-0.9) to 0.5 (95% CI, 0.3-1.0) per 10 000 first treatments. No events were identified at first dextran treatments. There were 231 294 first penicillin treatments with 30 potential cases of anaphylaxis (IP = 1.2; 95% CI, 0.8-1.7 per 10 000 treatments). CONCLUSION: We found an IP of anaphylaxis from 0.4 to 0.5 per 10 000 first IV iron treatments. The study captured only a fraction of IV iron treatments administered in hospitals, where most first treatments are likely to happen. Due to this limitation, the study could not exclude a differential risk of anaphylaxis between iron dextran and iron non-dextrans. The IP of anaphylaxis in users of penicillin was consistent with incidences reported in the literature.

Whole genome sequencing identifies genetic variants associated with co-trimoxazole hypersensitivity in Asians.

BACKGROUND: Co-trimoxazole, a sulfonamide antibiotic, is used to treat a variety of infections worldwide, and it remains a common first-line medicine for prophylaxis against Pneumocystis jiroveci pneumonia. However, it can cause severe cutaneous adverse reaction (SCAR), including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms. The pathomechanism of co-trimoxazole-induced SCAR remains unclear. OBJECTIVE: We aimed to investigate the genetic predisposition of co-trimoxazole-induced SCAR. METHODS: We conducted a multicountry case-control association study that included 151 patients with of co-trimoxazole-induced SCAR and 4631 population controls from Taiwan, Thailand, and Malaysia, as well as 138 tolerant controls from Taiwan. Whole-genome sequencing was performed for the patients and population controls from Taiwan; it further validated the results from Thailand and Malaysia. RESULTS: The whole-genome sequencing study (43 case patients vs 507 controls) discovered that the single-nucleotide polymorphism rs41554616, which is located between the HLA-B and MICA loci, had the strongest association with co-trimoxazole-induced SCAR (P = 8.2 × 10-9; odds ratio [OR] = 7.7). There were weak associations of variants in co-trimoxazole-related metabolizing enzymes (CYP2D6, GSTP1, GCLC, N-acetyltransferase [NAT2], and CYP2C8). A replication study using HLA genotyping revealed that HLA-B∗13:01 was strongly associated with co-trimoxazole-induced SCAR (the combined sample comprised 91 case patients vs 2545 controls [P = 7.2 × 10-21; OR = 8.7]). A strong HLA association was also observed in the case patients from Thailand (P = 3.2 × 10-5; OR = 3.6) and Malaysia (P = .002; OR = 12.8), respectively. A meta-analysis and phenotype stratification study further indicated a strong association between HLA-B∗13:01 and co-trimoxazole-induced drug reaction with eosinophilia and systemic symptoms (P = 4.2 × 10-23; OR = 40.1). CONCLUSION: This study identified HLA-B∗13:01 as an important genetic factor associated with co-trimoxazole-induced SCAR in Asians.

Safe dose reduction of steroid pre-medication for docetaxel in head and neck neoplasm treatment.

CONCLUSION: The results suggest that the rate of severe hypersensitivity reactions did not increase when the dexamethasone pre-medication dose was reduced to 11 mg prior to docetaxel infusion. OBJECTIVES: Dexamethasone is commonly used to prevent the adverse effects of docetaxel in head and neck neoplasm treatment. The recommended dexamethasone dose is 8 mg orally twice daily for 3 days for each injection of docetaxel. This pre-medication reduces the incidence of adverse effects to 1-2% of treated patients. However, many adverse events have been observed with long-term steroid use. In an attempt to balance the benefits and harms of steroid prophylaxis without affecting the safety of docetaxel, this study tried to reduce the duration and dose of dexamethasone. METHODS: In this study, a total of 336 patients underwent docetaxel-containing protocols (TP or TPF regimens) to treat head and neck neoplasms. Docetaxel was given in doses of 70 mg/m(2) once every 3 weeks. Dexamethasone (0.75 mg/tablet) pre-medication was given in different doses (45, 24, 18, and 11 mg); the minimum dose included 6 mg orally in the morning and 5 mg intravenously immediately before docetaxel infusion. RESULTS: Severe hypersensitivity reactions were experienced by none of 30 patients who received 45 mg (7.5 mg orally twice for 3 days) dexamethasone pre-medication in 125 cycles, none of 20 patients who received 24 mg (6 mg orally twice for 2 days) dexamethasone in 77 cycles, and none of 20 patients who received 18 mg (4.5 mg orally twice for 2 days) dexamethasone in 79 cycles. Three of 266 patients who received 11 mg dexamethasone in 1054 applications developed a severe hypersensitivity reaction with bronchospasm and hypotension, two of the 266 patients developed a severe rash, and four developed severe oedema.