Ideal proportion of the population to be patch tested: How many should we be doing?

BACKGROUND: How many patients should we be patch testing? A previous study suggested that the minimum proportion of a population to be patch tested for allergic contact dermatitis was 1:700 annually. OBJECTIVES: To evaluate if the current minimum rate for patch testing has changed over the 20 years since the previous study in order to maximize the value. METHODS: In cooperation with the British Society for Cutaneous Allergy, a proforma for collation of retrospective data between January 2015 and December 2017 was sent to patch-test centers in the United Kingdom (UK) and the Republic of Ireland (ROI). The number of positive tests was analyzed against the proportion of population tested to see what proportion of the population would yield the greatest number of positive results. RESULTS: Responses from 11 centers showed that the minimum number needed to patch test had increased to 1:550 per head of population per year using the current criteria. CONCLUSIONS: In agreement with previous studies, we should be patch testing more people than we are. We could reduce the threshold for referral of patients we patch test to derive the most benefit from this investigation.

Loss of the interleukin-6 receptor causes immunodeficiency, atopy, and abnormal inflammatory responses.

IL-6 excess is central to the pathogenesis of multiple inflammatory conditions and is targeted in clinical practice by immunotherapy that blocks the IL-6 receptor encoded by IL6R We describe two patients with homozygous mutations in IL6R who presented with recurrent infections, abnormal acute-phase responses, elevated IgE, eczema, and eosinophilia. This study identifies a novel primary immunodeficiency, clarifying the contribution of IL-6 to the phenotype of patients with mutations in IL6ST, STAT3, and ZNF341, genes encoding different components of the IL-6 signaling pathway, and alerts us to the potential toxicity of drugs targeting the IL-6R.

Contact allergy to essential oils cannot always be predicted from allergy to fragrance markers in the baseline series.

BACKGROUND: Essential oils are fragrance substances that are labelled on cosmetic products by their INCI names, potentially confusing consumers. OBJECTIVES: To establish whether contact allergy to essential oils might be missed if not specifically tested for. METHODS: We tested 471 patients with 14 essential oils and 2104 patients with Melaleuca alternifolia oil between January 2008 and June 2014. All patients were tested with fragrance mix I, fragrance mix II, hydroxyisohexyl 3-cyclohexene carboxaldehyde, and Myroxylon pereirae. Three hundred and twenty-six patients were tested with hydroperoxides of limonene and linalool. RESULTS: Thirty-four patients had a +/++/+++ reaction to at least one essential oil. Eleven had no reaction to any of the six marker fragrance substances. Thus, 4 of 11 positive reactions to M. alternifolia oil, 2 of 7 reactions to Cymbopogon flexuosus oil, 1 of 5 reactions to Cananga odorata oil, 3 of 4 reactions to Santalum album oil and 2 of 3 reactions to Mentha piperita oil would have been missed without individual testing. CONCLUSION: A small number of patients who are allergic to essential oils could be missed if these are not specifically tested. Labelling by INCI names means that exposure may not be obvious. Careful inspection of so-called 'natural' products and targeted testing is recommended.

Acute urticaria.

Acute urticaria is a common condition, which presents in all age groups and to multiple specialties. It may be a presenting symptom of anaphylaxis. The following article describes the epidemiology, etiology, clinical features, differential diagnosis, investigations, management, and prognosis of acute urticaria. Contact urticaria and angioedema without urticarial weals are not covered, as these are described elsewhere in this issue.

Roles of neutrophils in the regulation of the extent of human inflammation through delivery of IL-1 and clearance of chemokines.

This study examined the establishment of neutrophilic inflammation in humans. We tested the hypotheses that neutrophil recruitment was associated with local CXCL8 production and that neutrophils themselves might contribute to the regulation of the size of the inflammatory response. Humans were challenged i.d. with endotoxin. Biopsies of these sites were examined for cytokine production and leukocyte recruitment by qPCR and IHC. Additional in vitro models of inflammation examined the ability of neutrophils to produce and sequester cytokines relevant to neutrophilic inflammation. i.d. challenge with 15 ng of a TLR4-selective endotoxin caused a local inflammatory response, in which 1% of the total biopsy area stained positive for neutrophils at 6 h, correlating with 100-fold up-regulation in local CXCL8 mRNA generation. Neutrophils themselves were the major source of the early cytokine IL-1ß. In vitro, neutrophils mediated CXCL8 but not IL-1ß clearance (>90% clearance of ≤2 nM CXCL8 over 24 h). CXCL8 clearance was at least partially receptor-dependent and modified by inflammatory context, preserved in models of viral infection but reduced in models of bacterial infection. In conclusion, in a human inflammatory model, neutrophils are rapidly recruited and may regulate the size and outcome of the inflammatory response through the uptake and release of cytokines and chemokines in patterns dependent on the underlying inflammatory stimulus.

Chronic urticaria: aetiology, management and current and future treatment options.

Chronic urticaria is a common condition that can be very disabling when severe. A cause for chronic idiopathic urticaria (CIU) is only infrequently identified. Potential causes include reactions to food and drugs, infections (rarely) and, apart from an increased incidence of thyroid disease, uncomplicated urticaria is not usually associated with underlying systemic disease or malignancy. About one-third of patients with CIU have circulating functional autoantibodies against the high affinity IgE receptor or against IgE, although it is not known why such antibodies are produced, or how the presence of such antibodies alters the course of the disease or response to treatment. There are only a few publications relating to childhood urticaria, but it is probably similar to the adult form, except that adult urticaria is more common. The diagnosis is based on patient history and it is vital to spend time documenting this in detail. Extensive laboratory tests are not required in the vast majority of patients. Chronic urticaria resolves spontaneously in 30-55% of patients within 5 years, but it can persist for many years. Treatment is aimed firstly at avoiding underlying causative or exacerbating factors. Histamine H1 receptor antagonists remain the mainstay of oral treatment for all forms of urticaria. The newer low-sedating antihistamines desloratadine, fexofenadine, levocetirizine and mizolastine should be tried first. Sedating antihistamines have more adverse effects but are useful if symptoms are causing sleep disturbance. Low-dose dopexin is effective and especially suitable for patients with associated depression. There is controversy as to whether the addition of an histamine H2 receptor antagonist or a leukotriene antagonist is helpful. For CIU, second-line agents include ciclosporin (cyclosporine) [which is effective in approximately 75% of patients], short courses of oral corticosteroids, intravenous immunoglobulins and plasmapheresis, although the last two were found to be beneficial in small trials only. Treatments for CIU with only limited or anecdotal supportive evidence include sulphasalazine, methotrexate, stanazol, rofecoxib and cyclophosphamide. The efficacy of photo(chemo)therapy is controversial. Physical urticarias may respond to H1 receptor antagonists, although in delayed pressure urticaria, and cold, solar and aquagenic urticaria, the response may be disappointing. Second-line agents for physical urticarias vary depending on the urticaria and most have limited supportive evidence. The potential for spontaneous resolution, the variation in the disease activity and the unpredictable nature of the disease makes the efficacy of treatments difficult to assess.

Classification of anti-FcepsilonRI and anti-IgE autoantibodies in chronic idiopathic urticaria and correlation with disease severity.

BACKGROUND: Circulating autoantibodies against FcepsilonRI, IgE, or both occur in approximately one third of patients with chronic idiopathic urticaria (CIU), but not all autoantibodies initiate histamine release. OBJECTIVE: We sought to classify patients with CIU into subsets on the basis of serum bioactivity and immunoreactivity and to examine the relationship between newly defined subtype and disease severity. METHODS: Sera from patients with CIU (n = 78), dermog-raphism (n = 15), and cholinergic urticaria (n = 10) and sera from healthy subjects (n = 39) were analyzed by means of Western blot analysis for anti-FcepsilonRI autoantibodies and for histamine release from basophils and dermal mast cells. In vivo reactivity of autologous serum was tested by means of intradermal injection, and CIU severity was determined on the basis of clinical interview. RESULTS: We classified sera from patients with CIU into 5 subsets: immunoreactive histamine-releasing anti-FcepsilonRI autoantibodies (n = 20 [26%]); immunoreactive anti-FcepsilonRI autoantibodies without histamine-releasing activity (n = 12 [15%]); anti-IgE-like autoantibodies (n = 7 [9%]); serum containing a mast cell-specific histamine-releasing factor (n = 7 [9%]); and sera with no identifiable factor (n = 32 [41%]). Patients with serum histamine-releasing activity had more severe urticaria than patients without such activity. Positive skin test responses to autologous sera were associated with histamine-releasing anti-FcepsilonRI autoantibodies but not with non-histamine-releasing anti-FcepsilonRI autoantibodies. Neither healthy subjects nor patients with dermographism or cholinergic urticaria had his-tamine-releasing anti-FcepsilonRI autoantibodies. CONCLUSION: These data support the specificity of functional anti-FcepsilonRI autoantibodies to CIU. The identification of distinctive subsets of patients suggests that other pathogenic mechanisms occur in CIU in addition to direct ligation of FcepsilonRI by autoantibodies causing dermal mast cell degranulation. Elucidating these mechanisms might lead to new treatments for CIU.

Chronic urticaria.

UNLABELLED: Chronic urticaria has a spectrum of clinical presentations and causes. About 50% of patients with "idiopathic" disease have histamine-releasing autoantibodies in their blood. The term autoimmune urticaria is increasingly being accepted for this subgroup of patients, in whom immunosuppressive therapies may be appropriate if conventional approaches to management are unsuccessful. This article reviews the classification, causes, and management of chronic urticaria in light of recent advances in the understanding of its etiology. LEARNING OBJECTIVE: At the conclusion of this learning activity, participants should have up-to-date knowledge of the classification, assessment, and management of chronic urticaria and understand where the concept of autoimmune urticaria fits into existing frameworks.