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Background: Chronic Spontaneous Urticaria (CSU) is an immune-mediated skin disease that may require prolonged treatments. Currently, there are no recommendations for treatment discontinuation once CSU symptoms are controlled, particularly among patients primarily diagnosed with severe CSU. Objective: In this real-life study we aimed to describe our experience of omalizumab (Oma) treatment withdrawal in CSU and define biomarkers related to these outcomes. Methods: CSU patients followed at our allergy clinic from January 2016 to December 2022 were included. Response to Oma therapy, and Oma-withdrawal outcomes among patients who reached complete remission for >6 months were analyzed. Results: During the study period 192/335(%) CSU patients were categorized as severe-CSU and entitled to receive Oma according to our country's regulations. Of them, 131/192(68%) were considered "Oma-responders", and 95/131(72.5%) patients underwent gradual treatment withdrawal. Successful Oma-withdrawal was documented in 47/95(49.5%) whereas 48/95(50.5%) patients experienced flare and were defined as unsuccessful OMA-withdrawal. The first was associated with shorter disease duration 7.1 ± 7.4 years vs. 10.7 ± 9.4 (P = 0.042), lower baseline-IgE 81.6 ± 84.1IU/ml vs. 324.7 ± 555.9 (P = 0.005), and lower baseline-eosinophils count 131.4 ± 110.5 vs. 195.6 ± 98.4 (P = 0.043) in comparison to failure of Oma-withdrawal group. Conclusion: OMA may be successfully withdrawn in up to 50% of severe CSU patients following complete remission of disease symptoms, utilizing a gradual withdrawal protocol. Oma-withdrawal failure was linked with longer duration of disease as well as high IgE and eosinophil counts prior to initiation of Oma therapy. These parameters may enable the design of a treatment withdrawal algorithm.
RESUMO
Deserts are characterized by unpredictable precipitation and extreme temperatures. Their fauna and flora are sensitive to anthropogenic environmental changes, and often recover slowly from environmental disasters. The effects of oil spills on the biota of desert regions, however, have scarcely been studied. We predicted that terrestrial invertebrates suffer long-term negative effects from an oil spill, due to their close association with the substrate. Thus, we investigated the effects of two oil spills that occurred in 1975 and 2014 in the hyper-arid 'Arava desert (Israel), on a spider that constructs silk-lined nests in burrows in compact, sandy soil in this extreme desert habitat. The spider, Sahastata aravaensis sp. nov. (Filistatidae), is described herein. We assessed spider burrow abundance in plots located in oil-contaminated and nearby uncontaminated clean soil (control) areas over five consecutive years and measured habitat characteristics in these plots. In the laboratory, we determined the preference of individuals for clean vs. oil-contaminated soil as a resting substrate. Finally, as this species was previously undescribed, we added a new species description. The abundance of Sahastata was significantly lower in oil-contaminated plots, and this was the case in the 40-year-old oil spill (1975) as well as in the recent one (2014). In laboratory tests, spiders showed a significant preference for the clean soil substrate over the oil-contaminated substrate. In the field, soil crust hardness and vegetation density did not differ significantly between oil-contaminated and control plots, but these measures were highly variable. The burrows were significantly clustered, suggesting that the young disperse only short distances. In the laboratory adult spiders did not dig burrows, perhaps indicating that adults remain permanently in their natal burrows and that in the field they may use vacant burrows. We conclude that Sahastata populations were affected negatively by the oil spills and these effects were long-lasting. We propose that by monitoring their spatial distribution, burrow-dwelling spiders such as Sahastata can be used as effective bioindicators of soil pollution in desert habitats.
RESUMO
BACKGROUND: Chronic Spontaneous Urticaria (CSU) is a relatively common immune mediated disease that can be effectively treated nowadays. Nevertheless, for some patients remission cannot be achieved following current treatment recommendations, defined as resistant CSU (r-CSU). Treating r-CSU is challenging, and, currently, there are no recommended interventions. In this real-life study we describe successful therapy of 18 r-CSU patients using an "intensified protocol" of anti-IgE-antibody (omalizumab) concomitantly with an immunosuppressant. We defined the r-CSU phenotype and compared it to omalizumab-responsive CSU (Or-CSU) phenotype. METHODS: Clinical and serological data of 72 CSU patients (ie, 18 r-CSU and 54 age and sex matched Or-CSU) were retrospectively collected and analyzed. All patients were diagnosed with CSU for ≥6 months and treated at the Sheba Medical Center during 2013-2018. RESULTS: Of 289 CSU patients, 18 (6%) were diagnosed with r-CSU and treated with the "intensified protocol" including omalizumab and cyclosporine-A (16p), methotrexate (1p), and azathioprine (1p). Of which, 14/18 (78%) achieved complete remission, 2/18 (11%) partial remission, and 2/18 (11%) no remission. During follow-up no serious adverse events were documented. r-CSU patients received higher doses of antihistamine (p < 0.0001) and omalizumab (425 ± 58 mg/month vs. 283 ± 86 mg/month; p < 0.0001) compared to Or-CSU. The r-CSU phenotype was linked with concomitant autoimmunity (p = 0.0005) and a lower level of IgE prior to initiation of therapy (p = 0.027). CONCLUSION: r-CSU may be a distinct CSU phenotype characterized by severe disease, concomitant autoimmunity, and lower baseline-IgE levels (low "autoallergy"). An "intensified protocol" with omalizumab and an immunosuppressive agent was found to be efficacious and safe for r-CSU. Further larger studies are required to verify these results.
