Oral/sublingual Phleum pretense grass tablet (Grazax/Grastek) to treat allergic rhinitis in the USA

With the approval of two grass tablets and one ragweed tablet for sublingual immunotherapy (SLIT) by the US FDA in April 2014, the practice of allergy immunotherapy (AIT) in the USA has dramatically changed. Until this time, there were no approved allergen extracts for sublingual administration and physicians who prescribed SLIT for their patients did so without full knowledge of proper dosing or assurance of its safety. Now sublingual allergen tablets are available that have proven safe and effective doses. This article describes, in detail, the studies that have been conducted with a timothy grass SLIT tablet and draws some comparisons to the alternative 5-grass SLIT tablet. It also attempts to predict what will be the impact of the introduction of these tablets on the practice of AIT in the USA over the next few years.     

Hypersensitivities to non-steroidal anti-inflammatory drugs

NSAIDs are the most commonly used medications worldwide and are responsible for almost 25% of adverse drug reactions. Such reactions can have different manifestations and can be immunologic or non-immunologic. The diagnosis is primarily based on the medical history, which can be difficult in patients receiving multiple medications. Because skin testing and blood tests are not valid for NSAIDs reactions, confirmation requires an appropriately-designed challenge. The latter could be avoided when the history is obvious and the reaction is life-threatening. The challenge route can be oral, nasal, or bronchial. Avoidance of the causative NSAID, often associated with the avoidance of the cross-reacting preparations, is the cornerstone of management. In most cases, a safe substitute can be used. When treatment with the causative NSAID is necessary, titrated desensitization can be performed. This review discusses the classes of NSAIDs, mechanisms of their adverse reactions, manifestations, diagnosis, and management.     

The role of complement in neurological and neuropsychiatric diseases

The complement system is a major component of innate immunity and a potent driver of inflammation. It has key roles in host defense against pathogens but can also contribute to pathology by driving inflammation and cell damage in diverse diseases. Complement has emerged as an important factor in the pathogenesis of numerous diseases of the CNS and PNS, including infectious, autoimmune and degenerative disorders, and is increasingly implicated in neuropsychiatric disease. Establishing the roles and relevance of complement in disease pathogenesis has become ever more important in recent years as new drugs targeting the complement system have reached the clinic, and the potential for using complement analytes as disease biomarkers has been recognized. In this brief review, the author summarizes the evidence implicating complement in these diseases and outlines ways in which this new understanding can be used to aid diagnosis and improve outcome.     

A review of disease activity measures for psoriatic arthritis: what is the best approach?

The measuring tools for disease activity of rheumatoid arthritis have long been adapted for assessing the disease activity of psoriatic arthritis (PsA), particularly as regards peripheral arthritis. However, because of the multifactorial aspects and multiple domains of PsA, such as axial and peripheral joints, skin and nails, enthesitis and dactylitis, must also be considered when measuring activity. After the introduction of biologic agents, it became clear that more objective measuring tools were needed to assess the varied aspects of disease activity, as well as the effect of treatment. Collaborations among international groups of rheumatologists and dermatologists have helped define key or core domains of PsA that were recommended for inclusion in clinical trials and potentially clinical practice. Groups such as the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis have tried to develop and validate new outcome measures in PsA. Several new composite measures for specific PsA have been recently developed. The domains, instruments and traditional and new composite measures for PsA are reviewed herein.     

Interleukin-15 in the treatment of cancer

IL-15 is a 14–15 kDa member of the four α-helix bundle of cytokines that acts through a heterotrimeric receptor involving IL-2/IL-15R β, γc and the IL-15 specific receptor subunit IL-15R α. IL-15 stimulates the proliferation of T, B and NK cells, and induces stem, central and effector memory CD8 T cells. In rhesus macaques, continuous infusion of recombinant human IL-15 at 20 μg/kg/day was associated with approximately a 10-fold increase in the numbers of circulating NK, γ/δ cells and monocytes, and an 80- to 100-fold increase in the numbers of effector memory CD8 T cells. IL-15 has shown efficacy in murine models of malignancy. Clinical trials involving recombinant human IL-15 given by bolus infusions have been completed and by subcutaneous and continuous intravenous infusions are underway in patients with metastatic malignancy. Furthermore, clinical trials are being initiated that employ the combination of IL-15 with IL-15R α^+/- IgFc.     

Immunotherapy for non-small cell lung cancer: are we on the cusp of a new era?

In this editorial, we highlight the exciting advances in immunotherapy for the treatment of non-small cell lung cancer, with nivolumab being the first immunotherapeutic agent to be approved by the US FDA for the treatment of squamous lung cancer and several other promising immune checkpoint inhibitors currently being evaluated in clinical trials. The next step is to understand the mechanisms of resistance and develop rational combinations in an attempt to further improve the responses and survival in lung cancer.     

Topical nasal lysine aspirin in aspirin-sensitive and aspirin-tolerant chronic rhinosinusitis with nasal polyposis

Chronic rhinosinusitis patients with nasal polyps can be aspirin sensitive or aspirin tolerant. The majority belong to the latter group. They tolerate intake of aspirin or other non-steroidal anti-inflammatory drugs, whereas aspirin-sensitive patients have an adverse reaction (asthma, rhinitis and/or urticaria). Diagnosis of aspirin sensitivity is important for the patient, but is rarely undertaken in routine ENT or respiratory medicine practice. Treatment of nasal polyps is by a combination of medical therapy and surgery. Oral and topical steroids form the mainstay of medical therapy, which is aimed at reducing inflammation and symptom improvement. Surgery helps with polyps causing severe nasal obstruction. Despite these therapies, recurrences are common in aspirin sensitive patients. Any adjunctive therapy to prevent or prolong recurrence would be welcome. One such possibility is topical nasal lysine-aspirin. This is an area under current debate and this non-systematic review aims to provide evidence of its use, to date, in aspirin sensitive and aspirin tolerant nasal polyp patients.     

Genetic,genomic and epigenetic studies as tools for elucidating disease pathogenesis in primary Sjögren’s syndrome

Primary Sjögren’s syndrome (pSS) is characterized by lymphoid infiltration of lacrimal and salivary glands leading to xerophthalmia and xerostomia. pSS is a complex disease involving both genetic and environmental risk factors. Technological advances over the past 10 years have revolutionized genetics and genomics research enabling high-throughput characterization and analysis of DNA and RNA in patient samples on a genome-wide scale. Further, application of high-throughput methods for characterization of epigenetic variation, such as DNA methylation status, is increasingly being applied to AID populations and will likely further define additional risk factors for disease risk and outcome. Main results obtain in pSS through these various approaches are reviewed here.     

Canakinumab for gout: a specific,patient-profiled indication

The role of interleukin-1 (IL-1) in inflammation induced by crystals, and especially by monosodium urate crystals (MSUCs), has raised much interest in both basic and clinical investigation. Several drugs have been developed, and more are still in development, to block IL-1 driven inflammation, though to date only canakinumab (blocking IL-1β) has been labelled, yet limited to the European Union, with a restricted indication to treat episodes of acute inflammation (EAIs) in patients with gout in whom other therapeutic choices are unacceptable. Other medications developed for IL-1 blocking, such as anakinra and rilonacept, have been tested in gout patients in clinical trials, but lack label approval and may be further restricted to orphan indication in gout. Notwithstanding, the use of IL-1 blockade to prevent EAIs in gout looks promising, but no drug has yet obtained approval for such an indication.     

Immune mechanism–targeted treatment of experimental epidermolysis bullosa acquisita

Epidermolysis bullosa acquisita (EBA) is an autoimmune bullous dermatosis characterized by chronic mucocutaneous blistering caused by autoantibodies directed against type VII collagen. EBA causes a high morbidity and is difficult to treat. Model systems have significantly broadened our understanding of EBA pathogenesis, leading to the identification of numerous therapeutic targets. Of these, so far, a few have been evaluated for their therapeutic potential in preclinical models. In mice, EBA can be induced by transfer of anti-type VII collagen antibodies or by immunization with the protein. The latter model, immunization-induced EBA, is ideal to test drugs for their therapeutic efficacy. Here, mice with already established disease can be treated for prolonged periods. Albeit time consuming, results from immunization-induced EBA will pave the way for clinical application in patients. As the key pathogenic principle, that is, autoantibody-induced, leukocyte-mediated tissue injury and inflammation, is shared by other diseases, these findings may have translational applications beyond EBA.