BSACI guideline for the set-up of penicillin allergy de-labelling services by non-allergists working in a hospital setting.

The Standards of Care Committee of the British Society for Allergy and Clinical Immunology (BSACI) and a committee of experts and key stakeholders have developed this guideline for the evaluation and testing of patients with an unsubstantiated label of penicillin allergy. The guideline is intended for UK clinicians who are not trained in allergy or immunology, but who wish to develop a penicillin allergy de-labelling service for their patients. It is intended to supplement the BSACI 2015 guideline "Management of allergy to penicillin and other beta-lactams" and therefore does not detail the epidemiology or aetiology of penicillin allergy, as this is covered extensively in the 2015 guideline (1). The guideline is intended for use only in patients with a label of penicillin allergy and does not apply to other beta-lactam allergies. The recommendations include a checklist to identify patients at low risk of allergy and a framework for the conduct of drug provocation testing by non-allergists. There are separate sections for adults and paediatrics within the guideline, in recognition of the common differences in reported allergy history and likelihood of true allergy.

Chlorhexidine: an unrecognised cause of anaphylaxis.

Chlorhexidine is a highly effective antiseptic and disinfectant. In the past 20 years there has been a substantial increase in the number of chlorhexidine containing products used in healthcare. Anaphylaxis to chlorhexidine was first reported in 1984 and was almost always seen in men. However, in the last 4 years we have observed a surge in confirmed cases of anaphylaxis to chlorhexidine, with increasing numbers of female patients recently diagnosed. Yet, awareness of chlorhexidine as a cause of anaphylaxis is low because it is not a drug but a 'hidden' allergen, for example as a coating on medical devices such as central lines and urinary catheters. Patients will often have more than one allergic/anaphylactic reaction before the diagnosis is suspected. We have observed that there is poor recognition of an initial allergic reaction to chlorhexidine, which is well described. This, alongside poor labelling of chlorhexidine containing products, has resulted in further inadvertent exposure resulting in severe anaphylaxis. Prompt referral to a specialist allergy centre ensures appropriate investigations, diagnosis and management. Increasing awareness of the potential risk of life-threatening anaphylaxis associated with chlorhexidine use is vital, particularly in perioperative procedures. Healthcare workers are fundamental in avoiding and preventing further reactions to chlorhexidine containing products in patients diagnosed with anaphylaxis to chlorhexidine.

Aspirin-sensitive respiratory disease.

Aspirin-sensitive respiratory disease (ASRD) is a condition characterized by persistent and often severe inflammation of the upper and lower respiratory tracts. Patients develop chronic eosinophilic rhinosinusitis, nasal polyposis, and asthma. The ingestion of aspirin and other cyclooxygenase-1 (COX-1) inhibitors induces exacerbations of airway disease that may be life-threatening. Thus, aspirin sensitivity is a phenotypic marker for the syndrome, yet nearly all affected individuals can be desensitized by the administration of graded doses of aspirin, leading to long-term clinical benefits. Patients with aspirin sensitivity are often able to tolerate selective COX-2 inhibitors. The pathogenesis of ASRD is underpinned by abnormalities in eicosanoid biosynthesis and eicosanoid receptor expression coupled with intense mast cell and eosinophilic infiltration of the entire respiratory tract. This review focuses on the molecular, cellular, and biochemical abnormalities characterizing ASRD and highlights unanswered questions in the literature and potential future areas of investigation.

Perioperative Hypersensitivity Evaluation and Management: A Practical Approach.

Perioperative hypersensitivity (POH) is an uncommon, potentially life-threatening event. Identification of POH can be difficult given the lack of familiarity, physiological effects of anesthesia, draping of the patient during surgery, and potential nonimmunological factors contributing to signs and symptoms. Given the unique nature and large number of medications administered in the perioperative setting, evaluation of POH can be challenging. In this paper, we present a practical approach to management with an emphasis on understanding what happens in the operating room, the overlap of signs and symptoms between nonimmunological and immunological reactions, acute management, and subsequent evaluation. In addition, we provide a strategy for further review of an initially negative evaluation and emphasize the importance of establishing management plans for the patient as well as providing recommendations to the medical, anesthesia, and surgical teams for future surgeries. A critical factor for successful management at all points in the process is a close collaboration between the anesthesia and the allergy teams.

1α,25-dihydroxyvitamin D3 promotes CD200 expression by human peripheral and airway-resident T cells.

BACKGROUND: CD200, a cell-surface immunoglobulin-like molecule expressed by immune and stromal cells, dampens the pro-inflammatory activity of tissue-resident innate cells via its receptor, CD200R. This interaction appears critical for peripheral immune tolerance, particularly in the airways where excessive inflammation is undesirable. Vitamin D contributes to pulmonary health and promotes regulatory immune pathways, therefore its influence on CD200 and CD200R was investigated. METHODS: CD200 and CD200R expression were assessed by qPCR and immunoreactivity of human lymphoid, myeloid and epithelial cells following 1α,25-dihydroxyvitamin D3 (1α,25VitD3) exposure in vitro and in peripheral T cells following 1α,25VitD3 oral ingestion in vivo. The effect of 1α25VitD3 was also assessed in human airway-resident cells. RESULTS: 1α25VitD3 potently upregulated CD200 on peripheral human CD4+ T cells in vitro, and in vivo there was a trend towards upregulation in healthy, but not asthmatic individuals. CD200R expression was not modulated in any cells studied. CD200 induction was observed to a lesser extent in CD8+ T cells and not in B cells or airway epithelium. T cells isolated from the human airway also responded strongly to 1α25VitD3 to upregulate CD200. CONCLUSIONS: The capacity of 1α,25-dihydroxyvitamin D3 to induce CD200 expression by peripheral and respiratory tract T cells identifies an additional pathway via which vitamin D can restrain inflammation in the airways to maintain respiratory health.

Leukotriene E4: perspective on the forgotten mediator.

Leukotriene (LT) E(4) mediates many of the principal features of bronchial asthma, such as bronchial constriction, hyperresponsiveness, eosinophilia, and increased vascular permeability. Furthermore, it is the most stable of the cysteinyl leukotrienes (CysLTs) and can be active at the site of release for a prolonged time after its synthesis. There might be several reasons why LTE(4) has been forgotten. LTE(4) demonstrated low affinity for CysLT(1) and CysLT(2) receptors in equilibrium competition assays. It was less potent than other CysLTs in functional assays, such as calcium flux, in cells transfected with CysLT(1) and CysLT(2). The introduction of CysLT(1) antagonists into clinical practice diverted interest into CysLT(1)-related mechanisms, which were mediated mainly by LTD(4). However, experiments with animal models and human studies have revealed that LTE(4) has unique characteristics that cannot be explained by the current knowledge of CysLT(1) and CysLT(2). These activities include its potency relative to other CysLTs to increase airway responsiveness to histamine, to enhance eosinophilic recruitment, and to increase vascular permeability. Asthmatic airways also demonstrate marked in vivo relative hyperresponsiveness to LTE(4), especially in patients with aspirin-sensitive respiratory disease. This has stimulated a search for additional LT receptors that would respond preferentially to LTE(4) stimulation.