Neuropathic pain and itch: mechanisms in allergic conjunctivitis.

PURPOSE OF REVIEW: Allergic conjunctivitis is highly prevalent and affects up to one third of the general population. The current understanding of the pathophysiology and therapeutic strategies center around the type 2 inflammatory pathway. However, there is an increasing body of evidence that suggests neurogenic mechanisms also play a role in allergic inflammation, with a substantial proportion of allergic conjunctivitis patients experiencing both ocular itch and pain. RECENT FINDINGS: Unmyelinated C fibres on the ocular surface transmit histaminergic itch and can be directly activated by mast cell mediators. The conjunctival mucosa also contains TRPV1+ (histamine-dependent) and TRPA1+ (histamine-independent) neurons that enhance ocular pain and itch in allergic conjunctivitis. Allergen-complexed IgE also binds directly to FcεRI expressed on peripheral neurons. Environmental aeroallergens can also directly stimulate neuronal nociceptors to release inflammatory substances. Allergic inflammation thus stimulates nerve terminals to release vasoactive and inflammatory neuropeptides, leading to a cyclical neuronal dysregulation that augments mast cell activity. These repetitive cycles lead to both peripheral and central sensitization and neuronal plasticity, resulting in decreased itch/pain thresholds and a heightened itch/pain response. SUMMARY: Neurogenic mechanisms including peripheral and central sensitization may drive chronic ocular itch and pain secondary to allergic inflammation. Research into these pathways may help to identify therapeutic targets in allergic conjunctivitis patients with refractory symptoms.

Immediate Reactions After the First Dose of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Messenger RNA Vaccines Do Not Preclude Second-Dose Administration.

Addressing coronavirus disease 2019 (COVID-19) vaccine hesitancy and minimizing potential vaccine contraindications are critical to combatting the pandemic. We describe a practical approach to immediate adverse events after the first dose of messenger RNA vaccines for severe acute respiratory syndrome coronavirus 2, focusing on diagnosis and management of allergic reactions.

Approach to Perioperative Anaphylaxis in 2020: Updates in Diagnosis and Management.

PURPOSE OF REVIEW: The goal of the paper is to review the epidemiology, pathogenesis, diagnosis, and manifestations of perioperative anaphylaxis (POA). We seek to review the most common culprits of POA and different diagnostic modalities for evaluation. RECENT FINDINGS: Specific IgE testing has a limited role in POA evaluation due to lack of widespread availability and low sensitivity. Basophil activation testing is complementary to skin tests and can assist NMBA sensitivity diagnosis in complex cases. In the past years, there has been an exponential increase in suspected teicoplanin allergic reactions in the European Union. Chlorhexidine is also being increasingly implicated as a culprit in POA. Multiple classes of perioperative medications cause POA. Diagnostic modalities available include skin testing with nonirritating concentrations, basophil activation tests, specific IgE, and drug provocation testing. An accurate record and critical analysis of perioperative events is more important than isolated test results. Future studies evaluating the pathophysiology of these reactions and other therapeutic strategies, such as targeting the MRGPRX2 receptor, are needed.

The spectrum of allergic ocular diseases.

OBJECTIVE: The purpose of this article is to review the pathophysiologic mechanisms, differential diagnosis, evaluation, and treatment of the various manifestations of ocular allergy, with an especial focus on immunoglobulin E (IgE)-mediated disease. DATA SOURCES: A PubMed search was performed to include articles, using the search terms ocular allergy and allergic conjunctivitis. STUDY SELECTIONS: Recent and relevant human studies in the English language pertaining to our topic of study were selected. Animal studies pertaining to pathophysiology of ocular allergy were also reviewed. We focused on clinical trials, practice guidelines, reviews, and systematic reviews. In addition, case reports were reviewed if they described rare clinical presentations, disease mechanisms, or novel therapies. RESULTS: Ocular allergy encompasses both IgE- and non-IgE-mediated disease, and the clinical severity may range from mild to sight-threatening inflammation. A comprehensive treatment regimen including education, lifestyle measures, topical therapies, and even systemic interventions may be necessary for the effective management of ocular allergies, tailored according to symptom severity. CONCLUSION: Ocular allergy is frequently encountered by allergists and eye-care specialists, and despite progressively increasing incidence, it often remains underdiagnosed and, hence, untreated.

The Role of Mast Cells in Aspirin-Exacerbated Respiratory Disease (AERD) Pathogenesis: Implications for Future Therapeutics.

Mast cells (MC) have recently been demonstrated to play an integral role in the pathogenesis of aspirin-exacerbated respiratory disease (AERD). When activated, MCs release pre-formed granules of many pro-inflammatory mediators, including histamine, serotonin, and various chemokines and cytokines including tumor necrosis factor (TNF)-α, interferon É£ (IFN É£), macrophage inhibitory factor, transforming growth factor, interleukin (IL) 1, 3-6, 9, 10, 13 and 16. These mediators promote inflammation in AERD by recruiting or activating a network of cells involved in acute and chronic inflammatory pathways, such as endothelial, epithelial, stromal, and other immune cells. Several studies have implicated multifactorial pathways for MC activation in AERD beyond classical IgE mediated mechanisms. The elucidation of these complex networks therefore represents important targets for innovative patient therapeutics. This review summarizes classic and alternative pathways of MC activation in AERD with a special focus in relation to new and emerging treatment strategies.