Interleukin-6 and cytokine release syndrome: A new understanding in drug hypersensitivity reactions.

Immediate drug hypersensitivity reactions (DHRs) are historically thought to be because of immunoglobulin E (IgE) cross-linking, causing mast cell degranulation and release of mediators like tryptase and histamine. With the increasing use of monoclonal antibodies, it has become apparent that some patients present atypical features during immediate DHRs, including occurrence in initial exposure, a lack of urticaria and angioedema, and the presence of fever, chills, rigors and musculoskeletal pain as the predominant symptoms. This observation led to the recognition of a novel phenotype of immediate DHRs called cytokine release syndrome (CRS). Other types of immediate DHRs include infusion-related reactions (which present similarly to CRS), and mixed reactions (which share overlapping features of both type 1 reactions and CRS). Desensitization to culprit drugs can be a lifesaving option in patients who develop immediate DHRs to first-line treatment. Whereas robust data are supporting the safety and efficacy of drug desensitization, breakthrough reactions can still occur and CRS seems to be a more common cause than type 1 reactions. Tryptase has been the only available biomarker for immediate DHRs and is associated with type 1 reactions. Emerging evidence consistently found the association between increased serum interleukin 6 level and DHR-related CRS, suggesting that interleukin 6 can be a novel biomarker, in addition to tryptase, to distinguish various types of DHRs. In the era of precision medicine, phenotyping and endotyping hypersensitivity reactions to chemotherapy and monoclonal antibodies using validated biomarkers should be part of routine drug allergy care.

Drug hypersensitivity in the fast lane: What clinicians should know about phenotypes, endotypes, and biomarkers.

OBJECTIVE: To review novel concepts in drug hypersensitivity and the management of immediate hypersensitivity reactions. DATA SOURCES: English language literature on MEDLINE and Embase surrounding drug hypersensitivity and desensitization. STUDY SELECTIONS: References were selected based on relevance, date of publication, and originality. RESULTS: There are numerous citations looking at categorizing drug reactions, pathogenesis, biomarkers, and desensitization. Current understanding supports the use of a phenotype-endotype-biomarker model for categorizing immediate hypersensitivity reactions. Drug desensitization is a powerful therapeutic strategy that enables temporary induction of tolerance to medications that triggered immediate reactions. CONCLUSION: Immediate hypersensitivity reactions are diverse in presentation and pathogenesis. Drug desensitization is an effective intervention with sufficient evidence to support its more widespread availability.

In-center nocturnal hemodialysis.

Dialysis intensification from conventional regimens (typically thrice weekly, 4 hours per session) is increasingly utilized with the intent of improving the cardiovascular health and quality of life of chronic dialysis recipients. While home nocturnal hemodialysis offers the opportunity for maximal intensification of dialysis, it is inaccessible to the majority of dialysis recipients who are unable to self-administer hemodialysis in their own homes. In-center nocturnal hemodialysis (INHD) permits the intensification of conventional hemodialysis with the benefits of nursing support and supervision in addition to freedom from dialysis during productive daytime hours. Although no randomized trials have evaluated the relative merits of INHD, preliminary data indicate that INHD is a viable option that may confer a variety of benefits for chronic dialysis recipients.

Balancing Cancer Immunotherapy Efficacy and Toxicity.

Anti-programmed cell death-1 receptor/programmed cell death-1 receptor ligand-directed therapies are transforming cancer care, with durable antitumor responses observed in multiple cancer types. Toxicities arising from therapy are autoimmune in nature and may affect essentially any organ system. The immunologic basis of such toxities is complex, with contributions from T-cell activation and autoantibody generation. Although less recognized, hypersensitivity reactions are also possible. Although most toxicities resolve with systemic corticosteroids, some require second-line immunosuppression. Furthermore, the safety of drug rechallenge is not well characterized, with variable rates of toxicity flares arising with re-exposure. Herein, we review toxicities of immune checkpoint inhibitor therapies, particularly focusing on issues that allergists/immunologists may clinically encounter, including interstitial nephritis, skin toxicity, and risks associated with immunotherapy rechallenge.

Anaphylaxis following a transvaginal ultrasound.

Polyethylene glycol is a ubiquitous, water-soluble, organic compound found in a wide variety of commercially available products. While generally a benign substance, in rare instances, it can induce hypersensitivity reactions. Herein, we describe a case of anaphylaxis to polyethylene glycol-containing lubricating gel used for a transvaginal ultrasound. This case highlights the importance of early recognition of a rare cause of anaphylaxis that may occur in the health-care setting. It is of particular importance given the widespread use of similar lubricating materials in multiple practice settings for the use of internal examinations and ultrasonography.

The Association Between Conversion to In-centre Nocturnal Hemodialysis and Left Ventricular Mass Regression in Patients With End-Stage Renal Disease.

BACKGROUND: In-centre nocturnal hemodialysis (INHD, 7-8 hours/session, 3 times/week) is an increasingly utilized form of dialysis intensification, though data on the cardiovascular benefits of this modality are limited. METHODS: In this prospective cohort study, we enrolled 67 prevalent conventional hemodialysis (CHD, 4 hours/session, 3 times/week) recipients at 2 medical centres in Canada, of whom 37 converted to INHD and 30 remained on CHD. The primary outcome was the change in left ventricular mass (LVM) after 1 year as assessed by cardiac magnetic resonance imaging. Secondary outcomes included changes in serum phosphate concentration, phosphate binder burden, haemoglobin, erythropoiesis stimulating agent usage, and blood pressure. RESULTS: Conversion to INHD was associated with a 14.2 (95% confidence interval [CI] 1.2-27.2) g reduction in LVM as compared with continuation on CHD. This result was maintained after adjustment for baseline imbalances between the groups and in ancillary analyses. There was a trend toward a larger drop in systolic blood pressure (9.8 [95% CI, -1.4-20.9] mm Hg) among INHD recipients with a significant reduction in the number of prescribed antihypertensive agents (0.7 [95% CI, 0.3-1.1] agents). Serum phosphate declined by 0.40 (95% CI, 0.16-0.63) mmol/L among INHD recipients without any difference in calcium-based phosphate binder requirements, as compared with those who remained on CHD. CONCLUSIONS: Compared with continuation of CHD, conversion to INHD was associated with significant LVM regression and reduction in serum phosphate concentration at 1 year.

Methotrexate-induced pulmonary toxicity.

Methotrexate is a widely used medication with an array of recognized side effects. The present report describes a case of methotrexate-induced pneumonitis in a patient with psoriasis, and demonstrates the hallmark clinical and investigational findings that support this infrequently encountered diagnosis. The ensuing discussion reviews the pathogenesis, management and prevention of this adverse drug reaction.

Comparative assessment of 2-dimensional echocardiography vs cardiac magnetic resonance imaging in measuring left ventricular mass in patients with and without end-stage renal disease.

BACKGROUND: While echocardiography (ECHO)-measured left ventricular mass (LVM) predicts adverse cardiovascular events that are common in hemodialysis (HD) recipients, cardiac magnetic resonance imaging (CMR) is now considered the reference standard for determination of LVM. This study aimed to evaluate concordance between LVM measurements across ECHO and CMR among chronic HD recipients and matched controls. METHODS: A single-centre, cross-sectional study of 41 chronic HD patients and 41 matched controls with normal kidney function was performed to compare LVM measurements and left ventricular hypertrophy (LVH) designation by ECHO and CMR. RESULTS: In both groups, ECHO, compared with CMR, overestimated LVM. Bland-Altman analysis demonstrated wider agreement limits in LVM measurements by ECHO and CMR in the chronic HD group (mean difference, 60.8 g; limits -23 g to 144.6 g) than in the group with normal renal function (mean difference, 51.4 g; limits -10.5 g to 113.3 g). LVH prevalence by ECHO and CMR in the chronic HD group was 37.5% and 22.5%, respectively, while 17.5% and 12.5% had LVH by ECHO and CMR, respectively, in the normal kidney function group. Intermodality agreement in the designation of LVH was modest in the chronic HD patients (κ = 0.42, P = 0.005) but strong (κ = 0.81, P < 0.001) in the patients with preserved kidney function. Agreement was strong in assessing LVH by ECHO and CMR only in those with normal kidney function. CONCLUSIONS: Our results suggest that the limitations of LVM measurement by ECHO may be more pronounced in patients receiving HD, and provide additional support for the use of CMR in research and clinical practice when rigourous assessment of LVM is essential.