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维生素D 荨麻疹
维生素D与荨麻疹之间的关系已引起了越来越多的关注，尤其是在慢性荨麻疹（Chronic Urticaria, CU）患者中。荨麻疹是一种常见的皮肤疾病，特点是出现皮肤风团，伴有或不伴有血管性水肿，持续时间超过六周。慢性荨麻疹的病因通常不明确，但已有研究表明维生素D缺乏可能与此类皮肤病的发生和加重相关。
维生素D与慢性荨麻疹的关联
研究表明，慢性荨麻疹患者的血清维生素D水平通常显著低于健康对照组。一项系统评价与荟萃分析研究显示，慢性自发性荨麻疹患者的平均血清25(OH)D水平较低，且缺乏维生素D的情况在这些患者中更为普遍。而且，一些研究发现，维生素D水平与荨麻疹的病严重程度呈负相关，即维生素D水平越低，荨麻疹的症状越严重。
具体而言，根据研究，维生素D缺乏（通常定义为血清25(OH)D水平低于20 ng/mL）在慢性荨麻疹患者中表现得尤为突出，约34.3%至89.7%的患者存在此问题，而健康对照组的比例要低得多. 由此可以推断，充分的维生素D水平可能对于维持免疫系统的正常功能、减少炎症反应以及缓解荨麻疹的症状具有重要意义。
维生素D补充的潜在益处
一些小规模的研究探索了维生素D补充在慢性荨麻疹成为辅助治疗的潜力。比如，一项针对77名慢性荨麻疹患者的随机对照试验结果显示，经过高剂量的维生素D补充治疗，患者的血清维生素D水平显著上升，且症状评分也有明显改善. 其他研究也得出类似的结论，认为高剂量维生素D补充可能有助于改善一些慢性荨麻疹患者的病情。
此外，有研究指出，在接受维生素D补充治疗的患者中，血清中炎性标志物(如C反应蛋白和肿瘤坏死因子α)的水平显著降低，这提示维生素D可能通过调节炎症反应来减轻荨麻疹的症状。然而，需要注意的是，大多数研究的样本量较小，且缺乏长期效果的确证。因此，尽管已有的证据支持维生素D在慢性荨麻疹管理中的潜力，但仍需要更多大规模、长期的随机对照试验来进一步验证这种关系。
维生素D补充的推荐
基于现有的研究结果，医疗保健提供者可以考虑对慢性荨麻疹患者进行维生素D水平的评估，并在医生的建议下进行适当的维生素D补充. 理想情况下，维生素D的补充应与其他治疗措施（如抗组胺药和系统性类固醇）相结合，以实现更好的临床效果。同时，调整饮食结构可能也会对慢性荨麻疹有所帮助，例如，减少可能的食品过敏原或释放组胺的食物，以此来帮助减轻症状。
结论
总之，维生素D与慢性荨麻疹之间的关系是一个复杂且活跃的研究领域。虽然现有证据表明维生素D缺乏可能与慢性荨麻疹的发展和严重程度相关，且适量补充可能带来一定的益处，但尚需进一步深入的研究，以确立其在慢性荨麻疹管理中的具体作用和最佳使用方法。因此，对于慢性荨麻疹患者，关注维生素D的摄入和补充将是未来管理策略中的重要部分之一。
References
1Chronic Urticaria: Advances in Understanding of the Disease and Clinical Management.PubMed
Liting He, Wanyu Yi, Xin Huang, et al.
Chronic urticaria (CU) is a common skin condition characterized by the recurrence of wheals, with or without angioedema, which lasts for at least 6 weeks. Owing to its pruritus and incurability, this disease adversely affects the patients' physical and mental health and diminishes the quality of life. CU is generally classified into two subtypes based on the relevance of eliciting factors: chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU), the latter of which is further divided into several subtypes. To improve the understanding and clinical management of this highly heterogeneous disorder, the EAACI/GALEN/EDF/WAO guideline was developed and published in 2018 based on evidence and expert consensus. The diagnostic and treatment algorithms proposed by the guideline have largely facilitated dermatologists in clinical practice. However, several questions remained unsolved and have been widely investigated in the recent years. First, a better understanding of the association between chronic urticaria and its potential underlying causes or eliciting factors such as autoimmunity, infections, coagulation aberrance, and vitamin D deficiency is warranted. This would lead to updates in the diagnostic and treatment procedures of different subtypes of chronic urticaria. Secondly, treatment for recalcitrant cases, especially those resistant to or intolerant of second-generation antihistamines and (or) omalizumab, calls for novel therapeutic measures or strategies. In the present review, we summarized recent advances in the understanding and management of both CSU and CIndU, with special emphasis on their underlying causes or eliciting factors, pathogenic mechanisms, potential targets for intervention, and advances in treatment strategies.
2The association between serum vitamin D levels and urticaria: a meta-analysis of observational studies.PubMed
Xiaoyan Wang, Xiaorong Li, Yiwei Shen, et al.
INTRODUCTION: Despite the recent studies revealed Vitamin D may play a role in urticaria, no meta-analysis providing definite conclusions in this field has been reported. EVIDENCE ACQUISITION: A systematic search up to June 30th, 2017 was conducted in MEDLINE (via PubMed) and Excerpta Medica database (EMBASE) to identify relevant articles. Search terms included ''vitamin D'' or "25-hydroxyvitamin D" or "25-hydroxy-vitamin D" or "25(OH)D" or "1,25-dihydroxyvitamin D" combined with ''urticaria." EVIDENCE SYNTHESIS: Initial searches yielded 30 citations. Of these original results, 10 met specific selection criteria and were included in the meta-analysis with 547 urticaria cases and 517 controls. Vitamin D levels were significantly decreased in the urticarial cases (WMD -9.8 mg/L, 95% CI: -12.57 to -7.04 mg/L, from a random effects model), with a significant heterogeneity (I2=85.9%, P=0.000). When divide the Vitamin D level into two subgroups, the pooled OR comparing vitamin D insufficiency vs. normal level was 1.64 (95% CI: 0.71 to 3.77). Meanwhile, vitamin D deficiency vs. normal level was 4.09 (95% CI: 1.32 to 12.73). CONCLUSIONS: The study demonstrated that patients with urticaria had a lower Vitamin D level than healthy controls. Vitamin D deficiency rather than insufficiency has a positive relationship with urticaria. However, larger-scale studies with a longer duration of treatment are needed to confirm this conclusion.
3Nutrition and urticaria.PubMed
Kimberly Shao, Hao Feng
Urticaria is a distressing dermatologic condition for many. Although the wheals of urticaria are characteristically evanescent, lasting less than 24 hours, patients tend to have recurrent episodes. Hives that last less than 6 weeks are considered acute urticaria. Acute urticaria does not routinely require supplementary work-up because the history often identifies a convincing, inciting allergen. Chronic urticaria is defined as episodes that occur for longer than 6 weeks, and there is often not an easily identifiable trigger. For both acute and chronic urticaria, patients frequently report food as a precipitating cause. For acute urticaria, the foods that are associated with true allergies, such as nuts and shellfish, are the most frequent offenders. The relationship between diet and chronic urticaria is not as firmly defined. Many patients unnecessarily restrict their diets, so it becomes the role of dermatologists to help patients identify if there is a reproducible link between their symptoms and their dietary exposures. The literature suggests that diets free from pseudoallergens and histamine-releasing foods may attenuate urticaria. Supplements such as fats, vitamin D, iron, and flavonoids have also been studied and may diminish symptoms.
4Vitamin D supplementation: a potential booster for urticaria therapy.PubMed
Andy Rorie, Jill A Poole
Chronic urticaria is a common skin condition whereby the etiology remains largely idiopathic and the mainstay therapy is symptomatic control with antihistamines. There have been a limited number of small studies suggesting a potential role for vitamin D in chronic urticaria, and this this editorial review will discuss the current supporting evidence. Associations for decreased serum vitamin 25 hydroxyvitamin D levels in subjects with chronic urticaria have been reported. In addition to observational reports, there has been a randomized, prospective, blinded trial demonstrating symptom improvement when high vitamin D3 supplementation was utilized as an add-on therapy for urticarial management. More research is needed to address mechanisms of action and to investigate vitamin D supplementation in larger and longer duration human trials.
5Relationship between vitamin D and chronic spontaneous urticaria: a systematic review.PubMed
Papapit Tuchinda, Kanokvalai Kulthanan, Leena Chularojanamontri, et al.
BACKGROUND: Vitamin D has been reported to be associated with many allergic diseases. There are a limited number of the studies of vitamin D supplementation in patients with chronic spontaneous urticaria (CSU). This study aims to study the relationship between vitamin D and CSU in terms of serum vitamin D levels, and the outcomes of vitamin D supplementation. METHODS: A literature search of electronic databases for all relevant articles published between 1966 and 2018 was performed. The systematic literature review was done following Preferred Reporting Items for Systematic Reviews and Meta-analysis recommendations. RESULTS: Seventeen eligible studies were included. Fourteen (1321 CSU cases and 6100 controls) were concerned with serum vitamin D levels in CSU patients. Twelve studies showed statistically significant lower serum vitamin D levels in CSU patients than the controls. Vitamin D deficiency was reported more commonly for CSU patients (34.3-89.7%) than controls (0.0-68.9%) in 6 studies. Seven studies concerned with vitamin D supplementation in CSU patients showed disease improvement after high-dosages of vitamin D supplementation. CONCLUSION: CSU patients had significantly lower serum vitamin D levels than the controls in most studies. However, the results did not prove causation, and the mechanisms were not clearly explained. Despite the scarcity of available studies, this systematic review showed that a high dosage of vitamin D supplementation for 4-12 weeks might help to decrease the disease activity in some CSU patients. Well-designed randomized placebo-controlled studies are needed to determine the cut-off levels of vitamin D for supplementation and treatment outcomes.
6Efficacy and safety of active vitamin D supplementation in chronic spontaneous urticaria patients.PubMed
Amal Ahmed Mohamed, Maha S Hussein, Eman Mohamed Salah, et al.
BACKGROUND: Chronic spontaneous urticaria (CSU) is a common skin disorder affecting negatively patients' lives. Vitamin D deficiency has been reported to be associated to many allergic skin disorders. OBJECTIVE: This study aimed to evaluate the association between the serum level of 25 hydroxy vitamin D and CSU and to assess the efficacy and safety of active vitamin D in management of CSU. METHODS: The study was conducted on 77 patients with CSU and 67 healthy controls, then the 77 CSU patients were randomized to either the study group that received 0.25 µg alfacalcidol daily or the placebo group that received oral placebo for 12 weeks. RESULTS: Serum 25(OH) D was significantly lower in CSU as compared to healthy controls and was negatively correlated to the urticarial severity. After alfacalcidol administration, the study group showed significant higher level of 25(OH) D compared to the placebo group. In addition, the mean serum level of IL6, hsCRP and TNFα significantly decreased in the study group in comparison to the placebo group and as compared to their baseline results. CONCLUSION: Vitamin D deficiency is more common in CSU patients as compared to healthy people and hence, alfacalcidol might have a beneficial role as add on therapy in CSU management with no reported side effects.
7Chronic urticaria merits serum vitamin D evaluation and supplementation; a randomized case control study.PubMed
Roohi Rasool, Khalid Z Masoodi, Irfan A Shera, et al.
BACKGROUND: Several studies suggest that Vitamin D (Vit-D3) supplementation reduces Chronic Urticaria (CU) symptoms. OBJECTIVES: Evaluation of serum 25-hydroxyvitamin-D (25 (OH)2D) level and assessment of therapeutic effect of VitD3in CU patients. METHODS: 192 subjects were stratified according to the baseline 25(OH)2D levels and subsequently randomized into three subgroups to receive Vit-D3 alone (VD) or antihistamine and systemic corticosteroid (H+S) or VitD3 with antihistamine and systemic corticosteroid (VD+H+S) for 6 weeks between July 2012 to Oct 2014. 130 healthy controls (HC) were followed without any intervention. The patients were evaluated for reduction in urticarial symptoms using visual analogue scale (VAS) and 5-D itch score. RESULTS: Low serum levels of 25 (OH)2D was observed in 91% of CU patients and 64% of the healthy controls (P < 0.0001). VAS and 5-D Score in subgroups VD, H + S and VD + H + S decreased significantly from 6 · 7 ± 0 · 043, 6 · 6 ± 0 · 42 and 6 · 68 ± 0 · 40 at baseline to 5 · 2 ± 0 · 70 (P = 0 · 0088), 3 · 3 ± 0 · 50 (P < 0 · 0001) and1 · 86 ± 0 · 39 (P < 0 · 0001) after treatment and from 14 · 5 ± 0 · 72, 13 · 9 ± 0 · 77 and 13 · 9 ± 0 · 221 to 12 · 06 ± 1 · 10 (P = 0 · 0072), 8 · 1 ± 1 · 13 (P < 0 · 0001) and 5 · 01 ± 0 · 94 (P < 0 · 0001) respectively. CONCLUSIONS: CU patients have low serum 25(OH)2D levels and Vit-D3 supplementation in combination with antihistamine and systemic corticosteroid show elevated response in resolving the symptoms of CU. This study also warrants that each subject with CU should be screened for serum 25 (OH)2D levels before starting a treatment.
8Effects of Serum Vitamin D Levels and Vitamin D Supplementation on Urticaria: A Systematic Review and Meta-Analysis.PubMed
Yajia Li, Ziqin Cao, Jia Guo, et al.
(1) Backgrounds: Several studies have shown that the level of 25-hydroxyvitamin D (25(OH)D) could affect urticaria. The association of Vitamin D (VitD) with urticaria has not been well established. (2) Methods: The up-to-date meta-analysis was performed to synthesize the new findings. We performed a systematic search in PubMed, EMBASE, Web of Science, and Cochrane Database. We included the observational studies with the comparisons of 25(OH)D between urticarial populations and controls and clinical studies with the clinical severity of urticaria records. (3) Results: A meta-analysis of seventeen studies of urticaria group vs. controls revealed a mean difference of -9.35 ng/mL (95% CI -12.27 to -6.44). There was also an association of urticaria with VitD deficiency. In the subgroup analysis of age and disease type, significant effects of 25(OH)D were found among adult and chronic urticarial populations. Six VitD supplementation trials showed a significant reduction in clinical urticarial score on intervention with VitD with the standard mean difference of -3.63 and -1.54 among randomized control studies and repeated measure trials, respectively. (4) Conclusions: The urticarial population, especially the adult chronic urticarial patients, may be associated with a high risk for lower serum 25(OH)D. VitD supplementations could result in a reduction of urticarial clinical symptoms.
9Relationship between vitamin D status and the inflammatory state in patients with chronic spontaneous urticaria.PubMed
Alicja Grzanka, Edyta Machura, Bogdan Mazur, et al.
BACKGROUND: Chronic spontaneous urticaria (CSU) is an immune-inflammatory disease, characterized by acute phase response (APR) and immune activation. There has been increasing evidence showing that vitamin D deficiency/insufficiency is associated with increased incidence and/or severity of immune-inflammatory disorders. AIM: To assess relationship between vitamin D status and C-reactive protein (CRP), a nonspecific inflammatory marker of CSU activity. METHODS: Concentrations of CRP and 25-hydroxyvitamin D [25(OH)D], a biomarker of vitamin D status were measured in serum of CSU patients and compared with the healthy controls. RESULTS: Serum 25(OH)D concentration was significantly lower in CSU group as compared with the normal subjects. The prevalence of vitamin D deficiency (< 20 ng/ml) was significantly higher in patients with CSU than among normal population. There were no significant differences in prevalence of 25(OH)D insufficiency between the groups. Serum CRP concentrations were significantly higher in CSU patients as compared with the healthy subjects. There were no significant correlations between CRP and 25(OH)D concentrations in CSU patients. CONCLUSIONS: CSU is associated with lower serum 25(OH)D concentration and higher prevalence of its deficiency. The results failed to show any effect of vitamin D status on circulating CRP concentrations in CSU. A potential role of vitamin D in pathogenesis and/or additive therapy of CSU needs to be examined in other cohorts of CSU patients as well as in larger studies.
10Vitamin D as a Marker for Disease Severity in Chronic Urticaria and Its Possible Role in Pathogenesis.PubMed
Yu Ri Woo, Kyung Eun Jung, Dae Won Koo, et al.
BACKGROUND: Chronic urticaria is defined as repeated episodes of wheals lasting for 6 weeks or longer. Nowadays, the role of vitamin D in various chronic diseases is a matter of great interest, but limited data is available on the vitamin D status in patients with chronic urticaria. OBJECTIVE: The goal of this study was to investigate the relationship between vitamin D status and clinical characteristics of chronic urticaria. METHODS: The clinical records of 72 patients with chronic urticaria, 26 with acute urticaria and 26 with atopic dermatitis, along with 72 healthy controls, were retrospectively reviewed. RESULTS: The serum 25-(OH)D3 level was found to be significantly reduced in patients with chronic urticaria compared to those in the other groups. In particular, the proportion of patients with critically low vitamin D levels (<10 ng/ml) was significantly higher in the chronic urticaria group than in the other groups. The serum vitamin D levels showed significant negative associations with urticaria activity score and disease duration. In addition, serum vitamin D levels were significantly lower in subjects with a positive autologous serum skin test than in subjects with a negative result. CONCLUSION: In conclusion, the serum vitamin D level was more likely to be critically low in patients with chronic urticaria, and an inverse relationship with disease severity and disease duration was observed. These findings may open up the possibility of the clinical use of vitamin D as a contributing factor in the pathogenesis of chronic urticaria and a predictive marker for disease activity in chronic urticaria.