Therapeutic management of chronic spontaneous urticaria in clinical practice: results from a pilot survey.

BACKGROUND: The therapeutic approaches to patients with chronic spontaneous urticaria (CSU) differ among health care professionals and may be influenced by many factors. This cross-sectional survey was aimed at evaluating physicians' attitudes regarding therapeutic management of CSU in clinical practice. METHODS: A study-specific questionnaire was administered to a group of physicians (N.=21) with a specialist interest in CSU from different areas of Italy (group A) and also to other physicians (N.=25) who manage CSU only occasionally in their clinical activity (group B). RESULTS: In case of ineffectiveness of second-generation antihistamines at standard doses, higher doses of the same drug were always or frequently prescribed by most physicians in both groups, and 64% in group B and one third in group A usually increased the dose up to twice. Old-generation antihistamines were never used in clinical practice by 14% of survey participants in group A and 24% in group B, with the remaining physicians reporting rare or occasional uses. The prescription of systemic corticosteroids appeared to be more common among physicians in group B. The question concerning the use of alternative drugs in refractory CSU produced different answers between the two groups. Costs and access to specialist reference centers were indicated as the most important barriers to the use of medications different from antihistamines. CONCLUSIONS: These preliminary results suggest that therapeutic approaches to CSU seem to be heterogeneous in clinical practice and could be at least in part conditioned by the different medical settings where physicians usually work.

Angioedema associated with dipeptidyl peptidase-IV inhibitors.

BACKGROUND: Dipeptidyl peptidase-IV (DPP-IV) inhibitors, also known as gliptins, are a class of oral antidiabetic agents. Postmarketing reports have documented the occurrence of angioedema in patients treated with gliptins and it was found that these drugs increased the risk of angioedema in patients concurrently treated with angiotensin-converting enzyme inhibitors (ACEIs). The aim of this manuscript is to provide an overview of the risk of angioedema associated with gliptins. METHODS: The keywords used for the literature search in the PubMed database included "angioedema" and "dipeptidyl peptidase", "gliptins", or the name of each DPP-IV inhibitor. Articles in English published up to December 2020 were taken into consideration. RESULTS: The available data appear to rule out a higher risk of angioedema associated with gliptin monotherapy and have revealed an increased susceptibility in patients simultaneously treated with gliptins and ACEIs. However, one single multicenter phase IV trial and case reports, even if very limited in number, have shown that angioedema can also occur during treatment with DPP-IV inhibitors without the concomitant use of ACEIs. The involvement of other drugs and drug interactions has occasionally been suggested. In a few patients, deficiency of enzymes involved in bradykinin catabolism was detected and this finding can constitute a risk factor for angioedema exacerbated by treatment with DPP-IV inhibitors. CONCLUSIONS: This risk of angioedema associated with the use of gliptins has mostly been related to the concurrent administration of ACEIs, and has been considered rare, but it might be underestimated and underreported. The role of additional risk factors or drug interactions deserves further investigations. Caution should be taken when considering the use of DPP-IV inhibitors in patients treated with ACEIs or presenting with other known risk factors for angioedema.

Body Mass Index and Melanoma Prognosis.

INTRODUCTION: Obesity has been suggested as a risk factor in the progression of malignancies, including melanoma. Most studies defined obesity using body mass index (BMI), although the index is considered an imperfect measure of body composition. OBJECTIVE: The aim of this article is to examine whether BMI can impact on the prognosis of cutaneous melanoma, regardless of anti-tumor therapy. The relationship between BMI and specific prognostic factors in melanoma patients has been reviewed. METHODS: Literature search was conducted on PubMed using the terms "melanoma" and "body mass index" or "obesity". We selected articles, published up to 30 November 2020, examining the prognostic aspects of melanoma. Articles evaluating the risk and incidence of melanoma were excluded as well as studies regarding morbidity and complications following surgical procedures, or those performed in metastatic melanoma patients treated with anti-tumor therapies. RESULTS: Mixed results have emerged from studies assessing the clinical outcomes in melanoma patients in relation to BMI. More consistent data seem to support the relationship between BMI and Breslow thickness. CONCLUSIONS: Studies that focus specifically on the link between obesity and melanoma prognosis are limited; further research is needed to deepen our knowledge on this link.

Chronic spontaneous urticaria in clinical practice: a pilot survey about attitudes and perceptions on assessment, diagnostic work-up and dietary management.

BACKGROUND: Chronic spontaneous urticaria (CSU) is a heterogeneous condition whose management can be complex and challenging. The aim of this study is to evaluate physicians' attitudes regarding practical aspects of CSU management, including adherence to international guidelines, criteria and instruments for CSU assessment, prescription of laboratory investigations and role of dietary measures. METHODS: A cross-sectional survey was conducted using a study-specific questionnaire. It was administered to a group of physicians with a specialist interest in CSU from different areas of Italy definable as "CSU experts" (group A; N.=21) and subsequently to other physicians who managed CSU only occasionally in their clinical activity (group B; N.=25). RESULTS: The EAACI/GA2LEN/EDF/WAO guidelines were considered very or moderately useful by the majority of participants. Significantly more physicians in group A reported that such guidelines were always followed in clinical practice (P=0.0008). Instruments for the assessment of CSU severity/activity and quality of life were used in clinical practice significantly more often by CSU experts as compared to group B. Dietary measures were frequently suggested for CSU patients by nearly three quarters of group B members and by only 5% of CSU experts (P<0.00001). When physicians were asked to indicate the type of laboratory examinations that were commonly performed in patients with longstanding and/or uncontrolled CSU, regardless of history, the investigations most frequently reported were full blood count and thyroid autoantibodies, followed by erythrocyte sedimentation rate and/or C-reactive protein and thyroid function tests. CONCLUSIONS: The results of the present pilot survey seem to suggest the heterogeneity of the approaches used for CSU management in clinical practice.

Association Between Melanoma Risk and Height: A Narrative Review.

The link between anthropometric indices, including height, and cancer risk and/or progression has attracted considerable interest in recent years. Adult height results from the complex interplay between genetic, hormonal, nutritional, and other environmental factors and has been found to contribute to the risk of several selected malignancies, although it has not been implicated as a real cause per se. A number of studies have investigated the height-melanoma relationship, showing controversial results so far. In this review, we summarize the epidemiological data regarding the association between height and melanoma risk and analyze the potential underlying mechanisms.

Focus on the role of substance P in chronic urticaria.

BACKGROUND: Emerging data have strengthened the importance of substance P (SP) as a proinflammatory mediator in human pathology. A role for SP in the pathogenesis of urticaria has long been hypothesized. METHODS: Literature data regarding the possible role of SP in chronic urticaria/chronic spontaneous urticaria (CSU) have been reviewed and summarized in this manuscript. This review is based on pertinent articles that were retrieved by a selective literature search in the PubMed database. Articles in English published up to July 2018 were taken into consideration. RESULTS: Recent studies in patients with CSU have demonstrated that circulating levels of SP are significantly elevated, in correlation with disease severity, and that SP-positive basophils are upregulated. SP has been shown to trigger degranulation in basophils derived from CSU patients. Moreover, SP can be involved in pseudoallergic reactions and may act as a histamine-releasing factor in a subset of patients with CSU. Current evidence suggests that the biological activity of SP can be exerted not only through the conventional NK-1 receptor but also through the recently identified Mas-related G protein-coupled receptors. MRGPRX2 can cause mast cell activation and has been found to be upregulated in the skin of patients with severe chronic urticaria. CONCLUSIONS: Many findings seem to support the pathogenic involvement of SP in chronic urticaria/CSU. However, further studies are necessary to elucidate the role of SP as a mediator in CSU pathogenesis and a potential new therapeutic target.

Antihypertensive drugs and risk of skin cancer.

The potential carcinogenic risk of antihypertensive drugs has been examined in several studies that reported controversial results. The association between treatment with antihypertensives and risk of skin cancer has also been questioned, considering the long-term administration of such drugs and the ability of some agents to cause photosensitive reactions. In fact, experimental and epidemiologic findings suggest a link between drug-induced photosensitivity and skin cancer, possibly through the induction of DNA damage in predisposed individuals. Antihypertensive medications might influence skin homeostasis through additional mechanisms. For instance, some antihypertensive drugs can affect epidermal differentiation by interfering with calcium or sodium channels in the skin. Mediators in the renin-angiotensin system (RAS) are also involved in the modulation of cellular proliferation and angiogenesis. Of note, the existence of RAS has been recognized in many organs and tissues, including the skin. The available data regarding the relationship between use of different types of antihypertensives and skin cancer risk do not allow to draw definite conclusions at present. The aim of this article is to summarize the current evidence about the association of antihypertensive use with risk of non-melanoma skin cancer, melanoma, lip cancer and cutaneous lymphoma. A brief mention of the role of beta-blockers in melanoma progression has also been added.

Medication patterns in chronic spontaneous urticaria: results from a nationwide investigation in the primary care setting in Italy.

BACKGROUND: Only a few studies have assessed treatment usage in clinical practice among patients with chronic spontaneous urticaria (CSU). METHODS: The aim of this study was to evaluate patterns of medications used for CSU, analyzing the electronic patient records contained in the Italian general practice Health Search IMS Health Longitudinal Patient Database (HSD). The study period was from January 2002 to December 2013. RESULTS: The most frequent prescriptions during the year following CSU diagnosis were H1-antihistamines (78.47%) and corticosteroids (49.20%). Different medications were given to a limited number of CSU patients. CONCLUSIONS: The results of our study have shown that H1-antihistamines were the most prescribed drugs to treat CSU, reflecting their role as the mainstay of CSU treatment. Systemic corticosteroids continue to be frequently prescribed for CSU in clinical practice. Alternative drugs were used only in very few patients, suggesting the possibility that severe refractory cases of CSU are undertreated in clinical practice.

Alternative treatments for chronic spontaneous urticaria beyond the guideline algorithm.

PURPOSE OF REVIEW: The international EAACI/GALEN/EDF/WAO guideline suggests a stepwise approach for the therapeutic management of chronic spontaneous urticaria (CSU), outlined in an algorithm. The aim of this article is to summarize and review the evidence available on alternative treatment options for CSU outside of this algorithm. RECENT FINDINGS: Although CSU is a common disease, there are a limited number of high-quality studies, and only antihistamines and omalizumab are licensed for its treatment. Most studies regarding alternative therapies for CSU show methodological limitations and a high risk of bias. For many therapies, only case reports and uncontrolled studies exist. Recent publications on alternative treatments for chronic urticaria/CSU include reports on the use of adalimumab, rituximab, vitamin D, probiotics, histaglobulin, injection of autologous whole blood or serum, and phototherapy. SUMMARY: Numerous treatments beyond the guideline algorithm have been evaluated in patients with refractory CSU. The global level of evidence to support their efficacy in CSU is low or very low. Further research is needed to assess the efficacy and safety of alternative therapies of CSU to manage adequately those patients who do not respond to the treatments included in the algorithm.

Prescription Appropriateness of Cyproterone Acetate/Ethinylestradiol in Primary Care: A Population-Based Study in Italy.

BACKGROUND AND OBJECTIVE: We evaluated the prescription appropriateness of cyproterone acetate in combination with ethinylestradiol (CPA/EE) in a primary care setting before and after the 2013 European Medicines Agency's (EMA) recommendation relating to the risk profile of CPA/EE. METHODS: Data were obtained from the Health Search IMS Health Longitudinal Patient Database (HSD). We compared the results from 2011 to 2012 with the results of 2014, namely before and after the 2013 EMA recommendation, and investigated the burden of concurrent use of CPA/EE and other hormonal contraceptives (HCs) and the reported indication at the time of CPA/EE prescription. RESULTS: Overall, 1189 new users of CPA/EE were identified: 495 in 2011, 446 in 2012, and 261 in 2014. Concomitant use of CPA/EE and other HCs was found in 1% of cases in 2011-2012 and 2% of cases in 2014, while potential concomitant use was observed in 4% of cases in 2011 and 2% of cases in 2012 and 2014. A recent (within 365 days) diagnosis of any hyperandrogenic condition was detected in 22 and 24% of CPA/EE users in 2011 and 2012, respectively, and in 24% of cases in 2014. The percentage of CPA/EE users with a recent acne diagnosis and/or treatment was 19, 21, and 18% in 2011, 2012, and 2014, respectively. CONCLUSIONS: Apart from an overall reduction in CPA/EE prescriptions in the HSD, no substantial difference was found in terms of the proportions of patients diagnosed with acne or other hyperandrogenic conditions and/or potential concomitant use of HCs before and after the EMA recommendation.

Drug-induced eruptive melanocytic nevi.

INTRODUCTION: The sudden eruption of melanocytic nevi has been associated with a number of conditions, such as bullous skin diseases, immunodeficiency and immunosuppression. The exact mechanisms leading to the development of eruptive melanocytic nevi are unknown. Areas covered: The aim of this article is to review the literature concerning eruptive melanocytic nevi following the administration of immunosuppressive drugs and other medications. Expert opinion: The literature regarding the development of eruptive nevi in association with pharmacological therapies includes a relatively low number of reports. Prevalence of this phenomenon is likely to be underestimated, thus reporting should be encouraged in order to better define the actual significance and related clinical implications. The development of multiple melanocytic nevi during immunosuppressive treatments highlights the importance of immune system integrity in the regulation of nevi growth. The observation of eruptive nevi as an unexpected effect of targeted therapies for specific types of cancer, including melanoma, provided intriguing hints to understand the mechanisms underlying this paradoxical event. The synergistic role of additional triggers in the occurrence of drug-induced eruptive nevi has not been explored and may be an interesting area of research.

Current and future therapies for treating chronic spontaneous urticaria.

INTRODUCTION: Chronic spontaneous urticaria (CSU) is a disabling condition that causes deterioration of quality of life. AREAS COVERED: The international EAACI/GA(2)LEN/EDF/WAO guidelines have provided a stepwise treatment algorithm for CSU management. Second-generation H1-antihistamines are the first-line treatment, and the second step is the up-dosing of the same drugs. In refractory patients, the guidelines recommend the addition of omalizumab, ciclosporin A or montelukast. Systemic corticosteroids can be used as a short course during acute exacerbations. A plethora of alternative treatments has been evaluated, although the overall level of evidence for such treatments is low. Future treatment options may include inhibitors of skin mast cells and antagonists to mast cell-activating signals that are relevant for the induction of CSU signs and symptoms. EXPERT OPINION: The only licensed options included in the guidelines algorithm are standard-dosed second-generation H1-antihistamines and omalizumab. High-quality evidence has documented a rapid and strong symptomatic effect of omalizumab in CSU, although the optimal long-term regimens should be further investigated. The role of alternative drugs deserves additional studies. The potential of the existing treatments for inducing remission of CSU is unknown, and this is an important area of research, as is the evaluation of predictors of response, prognostic factors, and pathomechanisms.

Gender-related differences in chronic urticaria.

Chronic urticaria (CU) is a common skin disorder with important repercussion on the quality of life (QoL) and a relevant socioeconomic impact. CU is included among the skin diseases that exhibit a significant female preponderance, with an average female to male ratio of nearly 2-4/1. In recent years, an ever-growing interest in gender medicine has been registered and the assessment of gender differences has increasingly become an attractive issue in clinical research. Unfortunately, there are only limited data relative to the study of CU in the perspective of gender medicine. However, apart from the predilection for females, an in-depth evaluation of the available literature shows the existence of other interesting gender-related differences in CU. The aim of this article is to review the current knowledge on gender differences in CU under different points of view, including pathophysiology, epidemiology, clinical and prognostic features, association with comorbidities, psychological aspects and QoL.

Cyclosporine in psoriasis: comparison of a 25-year real-world Italian experience to current European guidelines.

Cyclosporine (CsA) is an effective and safe therapeutic option in various dermatoses in both adults and children. Over the last 25 years, Italian dermatologists have gained relevant experience about the use of CsA in the treatment of psoriasis and atopic dermatitis, and an Italian Consensus Conference has recently provided recommendations in adult patients. A comparison between these real-world indications and current European guidelines is hereby provided.

Daylight photodynamic therapy with methyl aminolaevulinate in patients with actinic keratoses: a preliminary experience in Southern Italy.

BACKGROUND: Daylight photodynamic therapy (D-PDT) is a novel modality of PDT in which the activation of the topical photosensitizer is mediated by the exposure to daylight instead of artificial light sources without the need of preliminary occlusion. This simplified modality has been found to be well tolerated. We report our experience with D-PDT in patients with actinic keratoses (AK). METHODS: The data relative to 53 patients consecutively treated for AK with a single session of D-PDT using methyl aminolaevulinate cream were retrospectively reviewed. Most patients had grade I and/or II AK on the face and/or the scalp. Some patients had additional cutaneous lesions, including non-melanoma skin cancers, in the AK-associated field, that were simultaneously treated with D-PDT. RESULTS: At 3 months, a complete response (AK number=0) was achieved by 54.7% of patients, and the lesion clearance rate was 82.7%. Treatment was more effective in thinner lesions, with complete clearance involving 93% of grade I AK. At 6-9 months after treatment, response was maintained in 85.7% of the lesions previously cleared, and 72.4% of the initial complete responders did not relapse. No relevant effect of D-PDT was instead observed on senile lentigo, nodular basal cell carcinoma and squamous cell carcinoma, whereas a complete response was seen in 7 of the 9 superficial basal cell carcinomas treated. Local skin reactions mostly consisted in slight erythema. Mild symptoms (burning and tingling sensations) were reported by 12 patients. CONCLUSIONS: These preliminary results support the favorable efficacy and tolerability profile of D-PDT, which seems to be an interesting, valid, and convenient therapeutic option for AK, and possibly also for superficial basal cell carcinomas.