Histologic studies of chronic idiopathic urticaria

Natbony, Sheila; Phillips, Murray G.; Elias, Jules M.; Godfrey, Henry P.; Kaplan, Allen P.

doi:10.1016/0091-6749(83)90096-9

Cited by 177 publications

(54 citation statements)

References 14 publications

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“…The hives last <24 h, with no skin lesion upon disappearance. However, interstitial oedema with a perivascular infiltrate containing lymphocytes, monocytes and eosinophils is observed in all cases [20]. Neutrophils and basophils may also be observed, and CD4 + T cells [21, 22] are also present.…”

Section: Resultsmentioning

confidence: 99%

Management of urticaria: not too complicated, not too simple

Ferrer

Bartra

Giménez‐Arnau

et al. 2015

Clin Experimental Allergy

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In spite of being an old disease and apparently easy to diagnose, chronic spontaneous urticaria (CSU) is still perceived as an uncontrollable and difficult to manage disease. The perception of the patient is that his/her condition is not well understood and that is suffering from a disorder with hidden causes that doctors are not able to tackle. Sometimes patients go through a number of clinicians until they found some CSU expert who is familiar with the disease. It is surprising that myths and believes with no scientific support still persist. Guidelines are not widely implemented, and recent tools to assess severity are infrequently used. European and American recent guidelines do not agree in several key points related to diagnosis and treatment, which further contributes to confusion. With the aim to clarify some aspects of the CSU picture, a group of allergists and dermatologists from the Spanish Dermatology and Allergy societies developed a Frequent Asked Questions leaflet that could facilitate physicians work in daily practice and contribute to a better knowledge of common clinical scenarios related to patients with CSU.

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Section: Resultsmentioning

confidence: 99%

Management of urticaria: not too complicated, not too simple

Ferrer

Bartra

Giménez‐Arnau

et al. 2015

Clin Experimental Allergy

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“…The latter possibility is of particular interest because some patients with chronic urticaria have basopenia [13]and their hyporesponsiveness to anti-IgE suggests in vivo desensitization [14]. Although migration of basophils into the skin of patients has been suggested as an explanation for these observations, there is no evidence of basophil accumulation within the skin [15, 16, 17]nor is there evidence of basopenia in allergic rhinitis or asthma where migration from the blood into involved tissue has been demonstrated to be a concomitant of the late phase reaction. In this manuscript we demonstrate elevated IL-4 levels in plasma of patients with chronic urticaria.…”

Section: Discussionmentioning

confidence: 99%

Secretion of Cytokines, Histamine and Leukotrienes in Chronic Urticaria

Ferrer¹,

Luquin²,

Sánchez-Ibarrola³

et al. 2002

Int Arch Allergy Immunol

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Background: Approximately 35–40% of patients with chronic urticaria have an IgG autoantibody to the IgE receptor which can activate basophils and mast cells so that they release histamine. In this study we assessed the cytokine profile present in chronic urticaria sera, and then measured cytokine and leukotriene release from basophils and mast cells upon incubation with chronic urticaria sera. Finally we assessed cytokine expression at the single-cell level and characterized the T cell subpopulations involved in their production. We chose IL-4 as representative of Th2 lymphocytes and IFN-γ for Th1 lymphocytes. Methods: We analyzed IL-4, IL-5 and IFN-γ in 60 chronic urticaria sera versus 51 controls. Sera were incubated with purified human basophils and cutaneous mast cells and the release of histamine, IL-4 and leukotrienes (C₄, D₄, E₄) was quantitated. Immunoblotting was performed to identify IgG antibody to FcΕRIα, α subunit. We measured intracellular cytokine production in peripheral blood mononuclear cells of 17 chronic urticaria patients compared to 50 healthy controls. Results: We found higher IL-4 levels (p = 0.028) in the sera of chronic urticaria patients (1.03 pg/ml) versus healthy donors (0.20 pg/ml) but no difference between urticaria sera and atopic control sera (0.52 pg/ml). We did not detect IFN-γ or IL-5 in any serum. However, sera that activated basophils so that they released histamine also produced leukotriene and IL-4, and leukotriene production by cutaneous mast cells and basophils was closely correlated. However, there was no correlation between immunoblotting and the functional ability to induce either histamine or IL-4. After stimulating with PMA-ionomycin we found significant differences in CD4+ lymphocyte production of IL-4 and IFN-γ with no differences in CD8+ lymphocyte production of either cytokine. Conclusion: Our data support the presence of basophil and mast cell activators in the sera of patients with chronic urticaria which can lead to the production of leukotrienes and IL-4 in addition to the histamine. IL-4 levels are similar to those seen in atopic subjects. We found that CD4+ T cells from patients with chronic urticaria are activated and tend to produce higher cytokine levels than CD4+ T cells from healthy controls. There were no differences when cytokine production by CD8+ lymphocytes was similarly assessed. These results are consistent with the histology found in biopsies of chronic urticaria lesions, where a CD4+-predominant infiltrate is found with cytokine production suggesting either a Th0 response or a mixture of Th1 and Th2 lymphocytes.

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“…Clearly histamine is a major contributor, but allergic or allergic-like disorders characterized by a prominent cellular infiltrate (either a late-phase reaction or comparable inflammatory response) often require additional approaches. The frequent requirement for corticosteroids to treat allergic rhinitis or asthma is a testament to that proposition, and the cellular infiltrate that characterizes chronic urticaria28-30 (a non-necrotizing perivascular infiltration of CD4+ lymphocytes, monocytes, neutrophils, eosinophils, and basophils) falls into that category. By contrast, dermatographism is an example of a histamine-mediated urticaria i.e.…”

Section: Treatmentmentioning

confidence: 99%

Treatment of Chronic Spontaneous Urticaria

Kaplan

2012

Allergy Asthma Immunol Res

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Chronic spontaneous urticaria is defined as persistent symptoms of urticaria for 6 weeks or more. It is associated with autoimmunity in approximately 45 percent of patients. Therapy is often difficult however the initial approach should employ high-dose non-sedating antihistamines; 4-6 tablets/day may be necessary. It has been shown that the response to 4 tablets/day exceeds 3, and exceeds 2, which exceeds 1. However the dose that corresponds to the maximal dose of first generation antihistamines (hydroxyzine, diphenhydramine) used previously, is 6/day. Yet over half the patients are refractory to antihistamines and other agents should be tried next. Whereas current guidelines (published) often add leukotriene antagonists and/or H2 receptor antogonists next, these are of little utility. Likewise drugs effective for urticarial vasculitis (colchicine, dapsone, sulfasalazine, hydroxychloroquine) are effective in a small percentage of patients and no study suggests that the response rate of any of them exceeds the 30% placebo responses seen in most double-blind, placebo controlled studies. The drugs that are effective for antihistamine-resistant chronic spontaneous urticaria are corticosteroids, cyclosporine, and Omalizumab. Use of steroids is limited by toxicity. If used at all, a dose of no more than 10 mg/day should be employed with a weekly reduction of 1 mg. The response rates to cyclosporine and Omalizumab are each close to 75%. Cyclosporine can be used effectively if care is taken to monitor blood pressure, urine protein, blood urea nitrogen, and creatinine, every 6 weeks. Omalizumab has the best profile in terms of efficacy/toxicity and, once approved by federal agencies for use in chronic spontaneous urticaria, a dramatic change in the treatment paradigm, whether associated with autoimmunity or not, is predicted. A phase 3 trial is currently in place. Refractoriness to both Omalizumab and cyclosporine is expected to be less than 5 percent of patients. Other agents, can then be tried.

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Histologic studies of chronic idiopathic urticaria

Cited by 177 publications

References 14 publications

Management of urticaria: not too complicated, not too simple

Management of urticaria: not too complicated, not too simple

Secretion of Cytokines, Histamine and Leukotrienes in Chronic Urticaria

Treatment of Chronic Spontaneous Urticaria

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