Alicja Grzanka

Relationship between vitamin D status and the inflammatory state in patients with chronic spontaneous urticaria

BackgroundChronic 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.AimTo assess relationship between vitamin D status and C-reactive protein (CRP), a nonspecific inflammatory marker of CSU activity.MethodsConcentrations 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.ResultsSerum 25(OH)D concentration was significantly lower in CSU group as compared with the normal subjects. The prevalence of vitamin D deficiency (< 20xa0ng/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.ConclusionsCSU 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.

Analysis of procalcitonin and CRP concentrations in serum of patients with chronic spontaneous urticaria

BackgroundOur previous findings showed the importance of analysing the peripheral markers of acute phase response (APR) activation, C-reactive protein (CRP) and IL-6 in the context of urticaria activity and severity. However, these biomarkers do not reliably differentiate between APR to infectious and the disease severity.AimIn order to investigate a possible association between the immune-inflammatory activation markers CRP and procalcitonin (PCT).MethodsSerum PCT and CRP concentrations were measured in patients with CU of varying severity as well as in healthy subjects.ResultsSerum PCT and CRP concentrations were significantly increased in more severe CU patients when compared to healthy controls and mild CU, and within the CU population there was a significant correlation between concentrations of PCT and CRP. Serum PCT concentrations remained within normal ranges in most CU patients and were only slightly elevated in some severe CU cases.ConclusionsPCT serum concentration may be only slightly elevated in some cases of severe CU. Upregulation of PCT synthesis accompanied by parallel changes in CRP concentration reflects a low-grade systemic inflammatory response in CU. PCT should be considered as a better marker than CRP to distinguish between APR to infection and an active non-specific urticarial inflammation.

Increased serum complement C3 and C4 concentrations and their relation to severity of chronic spontaneous urticaria and CRP concentration

Chronic spontaneous urticaria (CU) is associated with activation of the acute phase response (APR). Nevertheless, APR-associated proteins have not been well characterized as potential biomarkers of the disease severity. To assess the pattern of complement proteins C3 and C4 – the acute phase reactants in patients with CU. C3, C4 and CRP concentrations were measured in serum of 70 patients showing different degrees of urticarial severity as well as in 33 healthy subjects. Serum C3 and C4 concentrations were significantly increased in CU patients as compared with the healthy subjects and exceed the normal lab range by about 5% and 10%, respectively. Significant differences were found between patients with mild and increased CU severity. In addition, significant correlations were observed between C3, C4 and CRP concentrations. More severe CU is characterized by higher production of C3 and C4 complements accompanied by parallel changes in CRP concentration.

Pentraxin-3 as a local inflammatory marker in chronic spontaneous urticaria

BACKGROUNDnThe pentraxin family plays an important role in the acute phase response to immune-inflammatory processes. The short pentraxin, C-reactive protein (CRP) is a marker of chronic spontaneous urticaria (CSU) activity, reflecting the systemic effects of inflammatory mediators associated with the disease. It is known, that the long pentraxin, pentraxin 3 (PTX3) is produced at the sites of inflammation, therefore may better reflect activity of the local inflammatory processes. To assess the relevance of PTX3 in CSU patients and its association with CRP.nnnMETHODSnPlasma PTX3 and serum CRP concentrations were measured in patients with CSU of varying severity as well as in the healthy subjects.nnnRESULTSnThe concentrations of PTX3 and CRP were significantly increased in more severe CSU patients, when compared to mild CSU and the healthy controls. There was a significant correlation between concentrations of PTX3 and CRP.nnnCONCLUSIONSnIn contrast to CRP, PTX3 is produced at the sites of inflammation, therefore it seems that elevated PTX3 may result from activation of cells involved in local urticarial processes. Finally, the correlation between these two pentraxins suggests that they may be upregulated by the same mechanisms associated with acute phase response in CSU.

IL-6 Transsignaling in Patients with Chronic Spontaneous Urticaria

Background IL-6 trans-signaling is critically involved in the initiation and promotion of inflammatory and autoimmune diseases. Therefore, we investigated the clinical relevance of soluble members of IL-6 trans-signaling system in chronic spontaneous urticaria (CSU). Methods IL-6, interleukin 6 soluble receptor (IL-6 sR) and soluble gp130 (sgp130) were measured by ELISA method in plasma from CSU patients and the healthy subjects. The data were related to activation of the acute phase response as indicated by serum C-reactive protein (CRP) concentration and compared between patients stratified by the disease activity. Results Concentrations of IL-6, IL-6 sR, sgp130 in plasma and CRP in serum were significantly elevated in CSU patients compared with the healthy controls. CRP correlated significantly with IL-6 and sgp130, similarly IL-6 correlated significantly with sgp130. By contrast, CRP and IL-6 did not correlate significantly with IL-6 sR. However, significant correlation was noted between IL-6 sR and sgp130. Conclusions Concentrations of IL-6 and its soluble receptors were significantly elevated in patients with CSU, suggesting upregulation of the IL-6 trans-signaling in the disease. In addition, our results support the concept that the system may be involved in pathogenesis of the systemic inflammatory activation in CSU patients.

Effective treatment of different phenotypes of chronic urticaria with omalizumab: Case reports and review of literature

Despite the excellent efficacy and safety profile of omalizumab in chronic spontaneous urticaria (CSU), there are scarce data concerning its role in the treatment of refractory cases with different phenotypes of urticaria. We describe our experience with the therapy of nine patients with CSU co-existing with delayed pressure urticaria (DPU) or angioedema or both and refractory to treatment with high-dose antihistamines. The first patient, with severe CSU and recurrent angioedema, did not respond well to cyclosporine A or corticosteroids and suffered from numerous side effects of long-term corticosteroid therapy. The second patient presented with severe symptoms of DPU, which first of all prevented any daily activities of the professional routines. Both patients showed a complete remission of urticaria after the first injection of omalizumab. The third patient with CSU and severe DPU had been ineffectively treated for more than 20 years with various medications. Following the administration of omalizumab, the symptoms of CSU subsided but those of DPU intensified, and the drug was withdrawn after two cycles. In another four patients with refractory CSU and angioedema, the symptoms subsided after the first administration of omalizumab, and the patients have been in remission for about 5 weeks. In the remaining two patients, the symptoms did not resolve despite four 300 mg doses of omalizumab. It is important to establish a therapeutic regimen with omalizumab (150–300 mg; every 4–8 weeks) tailored to individual patient’s needs and dependent on the type of urticaria; this may minimize unnecessary the medication exposure, adverse drug effects, and healthcare costs.

The relationship between circulating concentrations of interleukin 17 and C reactive protein in chronic spontaneous urticaria

BackgroundUp-regulation of interleukin 17 (IL-17) family cytokines and acute phase response have been observed in patients with chronic spontaneous urticaria (CSU). It has been demonstrated that IL-17 stimulates C-reactive protein (CRP) expression.AimTo determine relationship between circulating concentrations of IL-17 and CRP in CSU.MethodsConcentrations of IL-17 in plasma and CRP in serum were measured in patients with CSU of varying severity and in the healthy subjects.ResultsIL-17 and CRP concentrations were significantly higher in CSU patients as compared to the healthy subjects. In addition, there were significant differences in IL-17 and CRP concentrations between CSU patients with mild, moderate-severe symptoms and the healthy subjects. CRP did not correlate significantly with IL-17.ConclusionsIncreased circulating IL-17 concentration may represent an independent index of systemic inflammatory response in CSU, which is not related to increased CRP concentration.

Refractory chronic spontaneous urticaria and permanent atrial fibrillation associated with dental infection: Mere coincidence or something more to it?

Controversy surrounds the role of dental infection/inflammation in the oral cavity in chronic spontaneous urticaria (CSU) and atrial fibrillation (AF), which is mainly due to scarce literature in this area. Therefore, this case report and review of literature illustrate a possible association between the acute-phase response (APR) and clinical conditions, such as CSU and dental infection/inflammation of oral cavity and AF. We describe a 36-year-old man with an 8-year history of difficult-to-treat, uncontrolled CSU, co-existent with dental infection/inflammatory processes of oral cavity and permanent atrial fibrillation (AF). In the presented case, the most likely triggering or aggravating/maintaining factor of the symptoms was the inflammation/dental infection of the oral cavity because of rapid reduction of the urticarial symptoms, drug doses, and serum CRP levels after the dental therapy. Dental treatment may have a beneficial effect on the systemic inflammatory response, reducing/normalizing the circulating levels of APR markers. APR activation appears to worsen CSU course, early identification and treatment of infectious/inflammatory foci in the oral cavity would form the mainstay of supportive therapy for CU probably through reduction of the systemic inflammatory burden. APR associated with infectious/inflammatory foci in the oral cavity could be taken into account as a predisposing agents to AF.

Circulating soluble receptor for advanced glycation end products is decreased and inversely associated with acute phase response in chronic spontaneous urticaria

BackgroundActivation of receptor for advanced glycation end products (RAGE) leads to the proinflammatory response and the release of its soluble form (sRAGE) which appears to function as an anti-inflammatory feedback mechanism.AimTo determine serum sRAGE concentration in CSU patients and its association with C-reactive protein (CRP) concentration, a nonspecific inflammatory marker of the disease activity.MethodsConcentrations of sRAGE and CRP were measured in serum of CSU patients and compared with the healthy controls.ResultsSerum sRAGE concentrations were significantly decreased in CSU patients, especially those more severely affected. In addition, significant inverse correlations were observed between sRAGE and CRP concentrations.ConclusionsDown-regulation of sRAGE and its association with acute phase response suggest a role for RAGE activation in the pathogenesis of CSU. It seems that lower serum sRAGE concentration may enhance the urticarial processes.

Hypersensitivity lo local anesthetics

Using local anaesthetics in daily practice, particularly by anaesthetists and dentists, is connected with the risk of side effects. Therefore, the observation of side effects, carrying out detailed research (according to the chart proposed in this study) and conducting specialist examinations is of the highest importance. There is a variety of side effects that could occur during local anaesthesia procedures, with the intensity ranging from clinically unimportant to life threatening. Clinicians major concerns are the appearance of various hypersensitivity reactions, including anaphylaxis. Healthcare providers responsible for the administration of local anaesthetics should be able to detect hypersensitivity reactions to implement appropriate treatment and then choose highly selected diagnostic procedures. The final diagnosis should be based on specific medical history; documentation, including a description of the case and measurement of tryptase activity; skin tests; and provocation trials. Screening tests are not recommended in populations without hypersensitivity to local anaesthestics in their medical history.