This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GA²LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), the European Dermatology Forum (EDF; EuroGuiDerm), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology with the participation of 64 delegates of 50 national and international societies and from 31 countries. The consensus conference was held on 3 December 2020. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell–driven disease that presents with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous or inducible urticaria is disabling, impairs quality of life, and affects performance at work and school. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert‐guided and evidence‐based diagnostic and therapeutic approaches for the different subtypes of urticaria.

We demonstrate for the first time that CU duration is associated with clinical parameters such as severity and angioedema, and with laboratory parameters such as autologous serum test and anti-thyroid antibodies. The ability to predict CU duration may facilitate decisions regarding the possible early initiation of cyclosporine A as a means by which to reduce disease severity and duration.

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Intravenous Ig therapy (IVIg) is reported to be a useful regimen in treating autoimmune diseases. In this study, we asked whether IVIg (in vitro) could increase the expression of TGF-β, IL-10, and the transcription factor FoxP3 in T regulatory (Treg) cells, and the idea that IVIg could enhance suppressive properties of these cells. CD4+ T cells from 12 healthy individuals were cultured in the presence or absence of IVIg vs human control IgG during 16, 24, and 36 h. Using FACS analysis and gating on CD4+CD25high Treg cells, we assessed the expression of intracellular TGF-β, IL-10, and FoxP3. In addition, the production of TNF-α by stimulated CD4+ T cells alone or in culture with CD25+ by itself or together with IVIg was also assessed. The presence of IVIg with Treg cells in culture significantly increased the intracellular expression of TGF-β (17.7 ± 8.5% vs 29.8 ± 13%; p = 0.02), IL-10 (20.7 ± 4.7% vs 34.2 ± 5.2%; p = 0.008) and FoxP3 (20.8 ± 5.2% vs 33.7 ± 5.9%; p = 0.0006) when compared with cells cultured alone or with control human IgG. The suppressive effect of CD4+CD25+ T cells presented as the decrease of TNF-α production by stimulated CD4+CD25− (effector T cells) was further increased by adding IVIg to cell culture. We hereby demonstrate an additional mechanism by which IVIg could maintain self-tolerance and decrease immune-mediated inflammation.

INTRODUCTION:To investigate whether immunologic factors in breast milk change in response to nursing infants' infection. RESULTS: Total cD45 leukocyte count dropped from 5,655 (median and interquartile range: 1,911; 16,871) in the acute phase to 2,122 (672; 6,819) cells/ml milk after recovery with macrophage count decreasing from 1,220 (236; 3,973) to 300 (122; 945) cells/ml. Tumor necrosis factor-α (TNFα) levels decreased from 3.66 ± 1.68 to 2.91 ± 1.51 pg/ml. The decrease in lactoferrin levels was of borderline statistical significance. such differences were not recorded in samples of the controls. Interleukin-10 levels decreased in the sick infants' breast milk after recovery, but also in the healthy controls, requiring further investigation. secretory immunoglobulin a levels did not change significantly in the study or control group. DISCUSSION: During active infection in nursing infants, the total number of white blood cells, specifically the number of macrophages, and TNFα levels increase in their mothers' breast milk. These results may support the dynamic nature of the immune defense provided by breastfeeding sick infants. METHODS: Breast milk from mothers of 31 infants, up to 3 months of age, who were hospitalized with fever, was sampled during active illness and recovery. Milk from mothers of 20 healthy infants served as controls.T he increased sensitivity of the newborn infant to infections originates from the immaturity of the immune system (1). In addition to transfer of immunoglobulin G to the fetus through the placenta, breastfeeding constitutes an important immunological support that the mammalian mother can provide to her relatively immunocompromised offspring against infections during the first months of life (2-6). The immune system in human milk includes secretory immunoglobulin A (sIgA), immunoglobulin G, free fatty acids, monoglycerides, proteins such as lactoferrin, lactalbumin, glycans, nonabsorbed oligosaccharides, exosomes, immunomodulators such as cytokines, nucleic acids, antioxidants, and immune cells such as macrophages, neutrophils, and lymphocytes (1,4,5,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). All these immunologic milk constituents interact together and with the newborn's gut directly or indirectly (e.g., by changing the gut flora) to increase immunity against infection, and probably also contribute to the maturation and efficiency of the newborn immune system (5,6).Many studies in both industrialized and developing countries have shown that nursing infants are less vulnerable to infections during their first months of life, including gastroenteritis, respiratory infections, otitis media, urinary tract infections, and necrotizing enterocolitis in premature infants (3,(18)(19)(20)(21)(22)(23)(24)(25).The mechanisms involved in the immunity provided by human milk to the nursing infant are not fully understood. Until recently, it was believed that the changes in immunological constituents of breast milk were mostly related to the time that elapsed from delivery or, in some cases,...

Older persons have higher autoimmunity but a lower prevalence of autoimmune diseases. A possible explanation for this is the expansion of many protective regulatory mechanisms highly characteristic in the elderly. Of note is the higher production of peripheral T-regulatory cells.The frequent development of autoimmunity in the elderly was suggested to take place in part due to the selection of T cells with increased affinity to self-antigens or to latent viruses. These cells were shown to have a greater ability to be pro-inflammatory, thereby amplifying autoimmunity. During aging, thymic T-regulatory cell output decreases in association with the loss of thymic capacity to generate new T cells. However, to balance the above mentioned autoimmunity and prevent the development of autoimmune diseases, there is an age-related increase in peripheral CD4+ CD25highFoxP3+ T-regulatory cells. It remains unclear whether this is an age-related immune dysfunction or a defense response. Whatever the reason, the expansion of T-regulatory cells requires payment in terms of an increased incidence of cancer and higher susceptibility to infections.

In a limited number of severe chronic idiopathic urticaria (CIU) patients, low-dose cyclosporin A (CsA) treatment was found to be effective. This open study aimed to extend this clinical observation and determine the safety of treatment with CsA. In addition, it aimed to determine the prevalence and characteristics of the autologous serum skin test (AST) in such patients, and whether this test is affected by CsA treatment. Thirty-five patients who suffered from severe CIU (score 3), and who were followed for 6 months (using a clinical urticaria-severity score [range 0-3]) were divided into three groups: 19/35 were treated for 3 months with low-dose CsA, and thereafter followed for an additional 3 months; 6/35 dropped out of protocol treatment; and 10/35 untreated patients (followed for the same period) served as a disease controls. In the treated group, no side-effects were observed, and by the end of treatment, 13/19 (68%) patients were in full remission (score 0) and the remainder scored 1. In contrast, the 10 CsA-untreated patients scored 3 for the whole follow-up period of 6 months. Positive AST was found in 14/35 (40%) of patients, whereas none were detected in 20 healty control subjects. AST neither correlated with disease activity nor predicted response to treatment. This uncontrolled study shows that low-dose CsA is effective in treating CIU patients, and can be given safely for 3 months. However, CIU patients requiring initially high doses of glucocorticosteroids and with a long clinical history are less amenable to CsA treatment.

Analysis of gene-targeted mice and patients with severe combined immunodeficiency due to mutations of the alpha chain of the interleukin-7 receptor (IL-7Ralpha) has shown important differences between mice and humans in the role played by IL-7 in lymphoid development. More recently, it has been shown that IL-7Ralpha is also shared by the receptor for another cytokine, thymic stromal lymphopoietin (TSLP). In this review, we discuss recent advances in IL-7- and TSLP-mediated signaling. We also report on the clinical and immunological features of 16 novel patients with IL-7Ralpha deficiency and discuss the results of hematopoietic stem cell transplantation.