Adverse infusion reactions to rituximab in systemic lupus erythematosus: a retrospective analysis.

BACKGROUND: To undertake a retrospective review of patients with SLE who had received Rituximab in order to determine the rates and associated patient characteristics of clinically significant adverse infusion reactions. METHODS: A descriptive analysis was undertaken of each infusion reaction, which was then assessed using the clinical information available to hypothesise on the possible underlying mechanism(s). RESULTS: Records of 136 SLE patients previously treated with 481 individual infusions of Rituximab were reviewed. A total of 22 patients (17.6%) had 28 (5.8% of total infusions) documented clinically significant adverse infusion reactions. Average age at first Rituximab infusion in patients without a reaction was 37 years (range 16-73) compared with 30 years (range 18-56) in those with a reaction. A high proportion of men (18.2%) experienced an infusion reaction. Severity and type of reaction varied. 6.4% of those who had a reaction were not retreated. CONCLUSIONS: While Rituximab remains an important tool in the treatment of SLE it is important to be aware that rates of infusion reactions may be more significant in SLE than in other diseases. A prospective study is required to better characterise the reactions.

Allergy test outcomes in patients self-reported as having penicillin allergy: Two-year experience.

BACKGROUND: Penicillin allergy is associated with increased antibiotic resistance and health care costs. However, most patients with self-reported penicillin allergy are not truly allergic. OBJECTIVE: To summarize our experience with allergy tests in patients with a history of penicillin allergy and to compare them with the results of other groups. METHODS: We retrospectively reviewed all patients with a suspected clinical history of penicillin allergy referred to the Drug Allergy Unit at University College London Hospital between March 2013 and June 2015. RESULTS: In total, 84 patients were reviewed. The index drugs included: unidentified penicillin (n = 44), amoxicillin (n = 17), amoxicillin-clavulanic acid (n = 13), flucloxacillin (n = 4), and other penicillins (ampicillin, benzylpenicillin, piperacillin-tazobactam; n = 7). Allergy diagnoses were confirmed in 24 patients (28.6%) (16 to penicillin, 3 to flucloxacillin, 5 to clavulanic acid). Twenty-two patients (91.7%) had allergy diagnosed by positive skin test results. Two patients (8.3%) developed IgE-mediated allergic symptoms during oral challenge (although the skin test results were negative). In vitro specific IgE test results for penicilloyl V, penicilloyl G, and amoxicilloyl were positive in 3 of 16 patients (18.8%). Moreover, reactions to cefuroxime were observed in 3 of 15 patients with penicillin allergy (20%). Selective clavulanic acid and flucloxacillin responders tolerated amoxicillin challenge. The interval between the index reaction and evaluation was shorter (P < .001), and the proportion of patients who could recall the name of the culprit drug was higher (P = .009) in the allergic group. Furthermore, histories of anaphylaxis (33.3%), urticaria, and/or angioedema (58.3%) were more common in the allergic group. Unspecified rashes (35.0%) and nonspecific symptoms (28.3%) predominated in the nonallergic group. CONCLUSION: Only 28.6% of patients with self-reported penicillin allergy were confirmed to be allergic. Importantly, when the index drug is amoxicillin-clavulanic acid or flucloxacillin, the patients may tolerate amoxicillin.

Treatment of Schistosomiasis in a Patient Allergic to Praziquantel: A Desensitization and Treatment Protocol.

Praziquantel is the mainstay of treatment of Schistosomiasis, which affects at least 262 million people worldwide. It is also used in the treatment of other trematode as well as cestode infections, with few safe and effective alternatives. It is generally well tolerated and allergic reactions are rare. In this report, we present a case of schistosomiasis with a history of a hypersensitivity reaction to praziquantel. Skin-prick and intradermal testing were performed, followed by treatment through rapid desensitization. This protocol may be of value to those patients requiring praziquantel treatment with a history of IgE-mediated allergy to the drug.

Real-time differential tracking of human neutrophil and eosinophil migration in vivo.

BACKGROUND: Hitherto, in vivo studies of human granulocyte migration have been based on indiscriminate labeling of total granulocyte populations. We hypothesized that the kinetics of isolated human neutrophil and eosinophil migration through major organs in vivo are fundamentally different, with the corollary that studying unseparated populations distorts measurement of both. METHODS: Blood neutrophils and eosinophils were isolated on 2 separate occasions from human volunteers by using Current Good Manufacturing Practice CD16 CliniMACS isolation, labeled with technetium 99m-hexamethylpropyleneamine oxime, and then reinfused intravenously. The kinetics of cellular efflux were imaged over 4 hours. RESULTS: Neutrophils and eosinophils were isolated to a mean purity of greater than 97% and greater than 95%, respectively. Activation of neutrophils measured as an increase in their CD11b mean fluorescence intensity in whole blood and after isolation and radiolabeling was 25.98 ± 7.59 and 51.82 ± 17.44, respectively, and was not significant (P = .052), but the mean fluorescence intensity of CD69 increased significantly on eosinophils. Analysis of the scintigraphic profile of lung efflux revealed exponential clearance of eosinophils, with a mean half-life of 4.16 ± 0.11 minutes. Neutrophil efflux was at a significantly slower half-life of 13.72 ± 4.14 minutes (P = .009). The migration of neutrophils and eosinophils was significantly different in the spleen at all time points (P = .014), in the liver at 15 minutes (P = .001), and in the bone marrow at 4 hours (P = .003). CONCLUSIONS: The kinetics of migration of neutrophils and eosinophils through the lung, spleen, and bone marrow of human volunteers are significantly different. Study of mixed populations might be misleading.

Imaging Inflammation in Asthma: Real Time, Differential Tracking of Human Neutrophil and Eosinophil Migration in Allergen Challenged, Atopic Asthmatics in Vivo.

BACKGROUND: It is important to study differential inflammatory cellular migration, particularly of eosinophils and neutrophils, in asthma and how this is influenced by environmental stimuli such as allergen exposure and the effects of anti asthma therapy. METHODS: We isolated blood neutrophils and eosinophils from 12 atopic asthmatic human volunteers (Group 1 - four Early Allergic Responders unchallenged (EAR); Group 2 - four Early and Late Allergic Responders (LAR) challenged; Group 3 - four EAR and LAR challenged and treated with systemic corticosteroids) using cGMP CD16 CliniMACS. Cells were isolated prior to allergen challenge where applicable, labelled with (99m)Tc-HMPAO and then re-infused intravenously. The kinetics of cellular influx/efflux into the lungs and other organs were imaged via scintigraphy over 4 h, starting at 5 to 6 h following allergen challenge where applicable. RESULTS: Neutrophils and eosinophils were isolated to a mean (SD) purity of 98.36% (1.09) and 96.31% (3.0), respectively. Asthmatic neutrophils were activated at baseline, mean (SD) CD11b(High) cells 46 (10.50) %. Isolation and radiolabelling significantly increased their activation to > 98%. Eosinophils were not activated at baseline, CD69(+) cells 1.9 (0.6) %, increasing to 38 (3.46) % following isolation and labelling. Analysis of the kinetics of net eosinophil and neutrophil lung influx/efflux conformed to a net exponential clearance with respective mean half times of clearance 6.98 (2.18) and 14.01 (2.63) minutes for Group 1, 6.03 (0.72) and 16.04 (2.0) minutes for Group 2 and 5.63 (1.20) and 14.56 (3.36) minutes for Group 3. These did not significantly differ between the three asthma groups (p > 0.05). CONCLUSIONS: Isolation and radiolabelling significantly increased activation of eosinophils (CD69) and completely activated neutrophils (CD11b(High)) in all asthma groups. Net lung neutrophil efflux was significantly slower than that of eosinophils in all asthma study groups. There was a trend for pre-treatment with systemic corticosteroids to reduce lung retention of eosinophils following allergen challenge.