A global perspective on stepping down chronic spontaneous urticaria treatment: Results of the Urticaria Centers of Reference and Excellence SDown-CSU study.

BACKGROUND: Although there have been significant advances in the treatment of chronic spontaneous urticaria (CSU) in recent years, there remains a lack of clear guidance on when and how to step down treatment in responders. This study aims to investigate stepping down approaches of different steps of CSU treatment from a global perspective. METHODS: "Stepping down chronic spontaneous urticaria treatment" (SDown-CSU) is an international, multicenter, observational, cross-sectional, survey-based study of the Urticaria Centers of Reference and Excellence (UCARE) network. The questionnaire included 48 questions completed by physicians in the UCARE network. RESULTS: Surveys completed by 103 physicians from 81 UCAREs and 34 countries were analyzed. Seventy-eight percent of the participants responded that they had a national urticaria management guideline written by their professional societies and 28% responded that they had to operate under a regulatory guideline proposed by central health funding organizations. Seventy-two and 58.7% of these national recommendations do not contain any detailed information on when and/or how CSU treatment should be discontinued. There was a lack of detailed information on antihistamines and cyclosporine in particular. A predefined maximum duration was generally not applicable to omalizumab and cyclosporine (81% and 82%, respectively). Nearly all UCAREs step down omalizumab within 6 months from the first controlled status and 42% discontinue cyclosporine after 6 months regardless of the control status. CONCLUSIONS: The findings from the SDown-CSU study clearly highlight a global need for guidance on the process of stepping down treatment in CSU. Additionally, the study offers a step-down algorithm applicable to all stages of CSU treatment.

Can Biologic Agents Improve Treatment Success in Obese Patients With Psoriasis Vulgaris: A Retrospective Review of 320 Patients With Psoriasis Vulgaris.

INTRODUCTION: Obesity plays a major role in the development of many inflammatory disorders including psoriasis. OBJECTIVES: We aimed to demonstrate how treatment responses change according to body mass index (BMI) among patients with psoriasis. METHODS: In our study, Psoriasis Area and Severity Index (PASI) 75 and PASI 90 responses were assessed at baseline and at months 1 and 3 among patients who received TNF-α inhibitors, ustekinumab, IL-17 blockers, and IL-23 blockers. The same responses were also assessed with methotrexate and acitretin for a comparison group. Analyses were performed retrospectively. RESULTS: The study included 317 patients who received 222 biological and 95 conventional treatments. In the group with BMI ≥30, the proportion of patients who achieved PASI 75 response was 40.0% (N = 26) at month 1 and 55.4% (N = 36) at month 3. The proportion of patients who achieved PASI 90 response was 33.8% (N = 22) at month 1 and 44.6% (N = 29) at month 3 among those receiving biological agents. Improvement was significantly more difficult among obese patients. The proportion of patients who achieved PASI 75 response was 3.6% at month 1 and 25.0% (N = 7) at month 3 among patients receiving conventional systemic treatments. While the presence of joint involvement affected the success of treatment among obese patients with psoriasis, no relationships were found for smoking, the presence of concomitant psychiatric diseases, or the presence of pruritus in psoriasis. CONCLUSIONS: Biological agents were more successful in achieving PASI 75 and PASI 90 responses in both non-obese and obese individuals. Based on our study, among biological agents, IL-17 and IL-23 inhibitors may be more successful among obese individuals, but neither of them shows superiority over the other.

In Chronic Spontaneous Urticaria, Complete Response to Antihistamine Treatment Is Linked to Low Disease Activity.

INTRODUCTION: The use of predictors of response to a specific treatment in patients with chronic spontaneous urticaria (CSU) can improve disease management, help prevent unnecessary healthcare costs, and save time. In this study, we aimed to identify predictors of complete response to standard-dosed and higher than standard-dosed antihistamine treatments in patients with CSU. METHODS: Medical records of 475 CSU patients, 120 of them <18 years old, from 3 different centers were analyzed. We used 15 machine learning (ML) models as well as traditional statistical methods to predict complete response to standard-dosed and higher than standard-dosed antihistamine treatment based on 17 clinical parameters. RESULTS: CSU disease activity, which was assessed by urticaria activity score (UAS), was the only clinical parameter that predicted complete response to standard-dosed and higher than standard-dosed antihistamine treatment, with ML models and traditional statistics, for all age groups. Based on ROC analyses, optimal cut-off values of disease activity to predict complete response were UAS <3 and UAS <4 for standard-dosed (area under the ROC curve [AUC] = 0.69; p = 0.001) and higher than standard-dosed (AUC = 0.79; p = 0.001) antihistamine treatments, respectively. Also, ML models identified lower total IgE (<150 IU/mL) as a predictor of complete response to a standard-dosed antihistamine and lower CRP (<3.4 mg/mL) as a predictor of complete response to higher than standard-dose antihistamine treatment. DISCUSSION: In this study, we showed that patients with UAS <3 are highly likely to have complete response to standard-dosed AH and those with a UAS <4 are highly likely to have complete response to higher than standard-dosed AH treatment. Low CSU disease activity is the only universal predictor of complete response to AH treatment with both ML models and traditional statistics for all age groups.

Eating Increases and Exercise Decreases Disease Activity in Patients With Symptomatic Dermographism.

BACKGROUND: Eating can increase disease activity in patients with symptomatic dermographism , the most common subtype of chronic inducible urticaria, but it is unclear how common this is. The effects of exercising on symptomatic dermographism disease activity have also not yet been determined. OBJECTIVE: To assess the impact of exercise and nonspecific carbohydrate-rich food intake on the severity and intensity of symptomatic dermographism after exercise and nonspecific carbohydrate-rich food intake. METHODS: We assessed disease activity by FricTest provocation testing in 75 symptomatic dermographism patients before and after eating, exercising, or both. We determined the rates of food-dependent (FD) symptomatic dermographism and food-exacerbated (FE) symptomatic dermographism. By comparing post- and pre-exercise FricTest scores, we identified complete responders: that is, patients with a negative FricTest response after exercising and partial responders. Finally, we evaluated whether exercise protects patients with FD-symptomatic dermographism or FE-symptomatic dermographism from eating-induced worsening of symptomatic dermographism. RESULTS: Of 64 symptomatic dermographism patients, eight had FD-symptomatic dermographism (13%), 42 had FE-symptomatic dermographism (66%), and 14 patients showed no negative impact of eating on disease activity (21%). Physical exercise reduced FricTest skin provocation test responses in 83% of 58 patients. Exercising protected patients with FD/FE-symptomatic dermographism from worsening of symptomatic dermographism owing to eating in half of cases, with higher rates for exercise after eating (67%) compared with exercise before eating (35%). CONCLUSIONS: Our study shows that eating often worsen symptomatic dermographism symptoms, and exercise often improves it. Our findings might aid patients in controlling symptoms better.

Survival of biological therapeutics in psoriasis: retrospective analysis of 3-years data in a Turkish registry, PSORTAKSIS.

BACKGROUND: TPSORTAKSIS is a psoriasis registry, which is used for follow-up of patients in Kayseri City Education and Research Hospital, Dermatology Clinic since 2016 in Turkey. PSORTAKSIS includes demographic data, follow-up clinical findings, laboratory output, and treatment information of patients. Here, drug survivals of biologic therapeutics (BT) according to three-year data of PSORTAKSIS will be presented. METHODS: Drug survival of BT in PSORTAKSIS was analyzed from 2016 to March 2019. RESULTS: 158 patients (111 of them BT-naive) with psoriasis under BT were enrolled in the current study. Drug survival analysis of patients with ongoing BT (158 treatment periods) revealed mean survival time as 15.49 months for ustekinumab, 15.37 months for adalimumab, 14.00 months for etanercept, 5 months for infliximab, and 4.59 months for secukinumab. The differences between drug survivals of BT were statistically significant (log-rank test, χ2 = 79.915, p < 0.0001).

Food-dependent and food-exacerbated symptomatic dermographism: New variants of symptomatic dermographism.

BACKGROUND: Symptomatic dermographism (SD) is the most common form of chronic inducible urticaria. The criterion standard for diagnosing SD and disease activity assessment in SD is provocation testing. As of now, if and what cofactors have an impact on provocation test results is unknown. OBJECTIVE: We sought to determine whether the induction of signs and symptoms of SD is affected by the intake of food. METHODS: We performed standardized skin provocation testing with a dermographometer (FricTest) before and after the intake of food. Patients were off antihistamine treatment for at least 3 days before testing. In total, 17 patients were tested after not having eaten for at least 4 hours (preprandial) on one volar forearm and 60 minutes after a carbohydrate-rich meal (postprandial) on the other. FricTest responses (wheals, itch) at trigger thresholds were assessed at 5 and 30 seconds as well as at 1, 2, 5, and 10 minutes. RESULTS: We identified 7 patients with SD who showed faster onset of FricTest-induced whealing and/or lower trigger thresholds after the intake of food, that is, food-exacerbated SD. In 5 other patients, FricTest provocation testing resulted in a positive response only after the intake of food, but not before. Three of these 5 patients with food-dependent SD had comorbid chronic spontaneous urticaria and 1 had cholinergic urticaria. CONCLUSIONS: We describe 2 previously unknown subtypes of SD, food-exacerbated SD and food-dependent SD. The prevalence and underlying pathomechanisms of food-exacerbated SD and food-dependent SD need to be investigated, and the impact of food intake on other forms of chronic inducible urticaria should be explored.

The COVID-19 Pandemic Affects Male Patients With Chronic Spontaneous Urticaria More Than Female Patients.

Introduction: The COVID-19 pandemic dramatically disrupts health care for patients with chronic diseases including chronic spontaneous urticaria (CSU). As of now, it is unknown if the effects of the pandemic in CSU are different than in other chronic diseases. We also do not know, if different groups of CSU patients, for example female and male patients, are affected differently. Aim: To understand how CSU patients and subgroups are affected by the COVID-19 pandemic in their disease activity and control and treatment, using psoriasis as control. Patients and Methods: We analyzed 399 patients (450 visits) with CSU or psoriasis assessed during August 2019, i.e. before the pandemic, or August 2020, i.e. during the pandemic, for changes in disease activity, disease control, and the treatment they used, and how these changes are linked to age, gender, and disease duration. Results: Male but not female patients with CSU had markedly increased disease activity during the pandemic. CSU patients' age or disease duration were not linked to changes. Male and female patients with psoriasis showed similar increases in disease activity and decreases in disease control. The rate of omalizumab treatment, during the pandemic, was unchanged in male patients and increased in female patients with CSU. The efficacy of omalizumab treatment, during the pandemic, was reduced in male patients but not female patients with CSU. Conclusion: Male but not female CSU patients, during the COVID-19 pandemic, show loss of disease control linked to loss of omalizumab efficacy. The reasons for this need to be investigated.

Fatigue Is Common and Predicted by Female Gender and Sleep Disturbance in Patients with Chronic Spontaneous Urticaria.

BACKGROUND: Fatigue is a common and disabling symptom in chronic inflammatory diseases. To the best of our knowledge, there are no studies evaluating fatigue thoroughly in patients with chronic spontaneous urticaria (CSU). OBJECTIVES: To evaluate fatigue and its drivers in patients with CSU, and to compare patients with healthy controls in terms of fatigue. METHODS: One hundred and three patients with CSU and 35 age- and gender-matched healthy control subjects were evaluated for fatigue with the Fatigue Severity Scale (FSS) and visual analog scale-fatigue. Patients were also assessed for their duration, activity, and control of disease, as well as anxiety, depression, and quality of life (QoL). RESULTS: There were no significant associations between disease activity, disease control scores, and FSS (P > .05). Although there were no significant differences in terms of antinuclear antibody positivity and IgE levels between fatigued and nonfatigued patients with CSU, C-reactive protein levels were higher in fatigued patients (P = .009). A significant correlation was noted between total FSS score and both Chronic Urticaria-QoL (r = 0.246, P = .013) and Dermatology Life Quality Index (r = 0.302, P = .002) in patients with CSU. In regression analyses, female gender and the presence of disturbed sleep were found to be significant predictors of fatigue in patients with CSU (P = .008; odds ratio [OR]: 9.02, and P = .001; OR: 8.35). CONCLUSION: Fatigue is a common and important symptom in patients with CSU and adversely affects QoL. While evaluating patients with CSU, it is important to assess fatigue, especially in female gender patients and in those having sleep disturbance.

The global impact of the COVID-19 pandemic on the management and course of chronic urticaria.

INTRODUCTION: The COVID-19 pandemic dramatically disrupts health care around the globe. The impact of the pandemic on chronic urticaria (CU) and its management are largely unknown. AIM: To understand how CU patients are affected by the COVID-19 pandemic; how specialists alter CU patient management; and the course of CU in patients with COVID-19. MATERIALS AND METHODS: Our cross-sectional, international, questionnaire-based, multicenter UCARE COVID-CU study assessed the impact of the pandemic on patient consultations, remote treatment, changes in medications, and clinical consequences. RESULTS: The COVID-19 pandemic severely impairs CU patient care, with less than 50% of the weekly numbers of patients treated as compared to before the pandemic. Reduced patient referrals and clinic hours were the major reasons. Almost half of responding UCARE physicians were involved in COVID-19 patient care, which negatively impacted on the care of urticaria patients. The rate of face-to-face consultations decreased by 62%, from 90% to less than half, whereas the rate of remote consultations increased by more than 600%, from one in 10 to more than two thirds. Cyclosporine and systemic corticosteroids, but not antihistamines or omalizumab, are used less during the pandemic. CU does not affect the course of COVID-19, but COVID-19 results in CU exacerbation in one of three patients, with higher rates in patients with severe COVID-19. CONCLUSIONS: The COVID-19 pandemic brings major changes and challenges for CU patients and their physicians. The long-term consequences of these changes, especially the increased use of remote consultations, require careful evaluation.

Effectiveness of as-needed antihistamines in chronic spontaneous urticaria patients under omalizumab treatment.

The question how second-generation antihistamines (sgAHs) should be used when chronic spontaneous urticaria (CSU) is under control with omalizumab is still unanswered. This study aimed to investigate the effectiveness of as-needed sgAHs in patients with well-controlled urticaria under omalizumab treatment. Patients from four different urticaria centers who were treated with omalizumab 300 mg/4 weeks for at least 3 months, had well-controlled urticaria (Urticaria Control Test: 16 > UCT≥12) and were using sgAHs only if needed, were included in this study. In order to assess effectiveness of sgAHs, change in the itch, hives, and total itch-hives scores before and after sgAHs were evaluated using modified urticaria activity score-twice daily. Fifty-three patients [38 female (71.7%)] with mean age 41.1 ± 11.4 years were included in this study. Median sgAH intake per patient throughout the 4 week-intervals was 3 (2-5) tablets. sgAH intake decreased itch, hives and total itch-hives scores 45.7% ± 52.9, 42.4% ± 39.1, and 50.2% ± 51.1, respectively (P < .001 for all). This decrease was similar in both isolated-urticaria and urticaria-and-angioedema phenotypes. Baseline IgE levels were positively correlated with the decrease of three symptom scores (r = 0.31, P = .05; r = 0.375, P = .017; r = 0.31, P = .05, respectively) that showed in patients with higher baseline total IgE levels, as needed sgAH intake decreased the symptom scores less. Our study showed that sgAHs may still be an effective option for the treatment of the intermittent symptoms in patients with well-controlled urticaria under omalizumab treatment. Baseline total IgE levels may be used as a potential biomarker for sgAH effectiveness in these patients.

Tofacitinib Induced Psoriasiform Lesion in a Patient With Rheumatoid Arthritis.

Paradoxical psoriasis or psoriasiform lesion is an adverse effect, represented by the occurrence of a psoriasiform lesion or exacerbation of psoriasis caused by the drugs normally used for the management of psoriasis. In this article, we present the first case of a 45-year-old male patient with rheumatoid arthritis who developed psoriasiform lesions following treatment with tofacitinib, and highlight the possible pathogenetic mechanisms involved in such an occurrence.

Sexual Functioning Is Frequently and Markedly Impaired in Female Patients with Chronic Spontaneous Urticaria.

BACKGROUND: Chronic spontaneous urticaria (CSU) is common, chronic, and debilitating, and has serious effects on quality of life and mental health. Three of 4 patients with CSU are women. The impact of CSU on female sexual functioning remains largely unknown. OBJECTIVE: To determine the prevalence of sexual dysfunction in female patients with CSU and to characterize their impairment of sexual functioning and its drivers. METHODS: Fifty-six female patients with CSU and 55 female aged-matched healthy control subjects were evaluated for sexual functioning with the Female Sexual Function Index. Patients were also assessed for their duration, activity, and control of disease, as well as angioedema, anxiety, depression, fatigue, and quality-of-life impairment. RESULTS: Sexual functioning, that is, total Female Sexual Function Index scores and all subscores, was markedly reduced in female patients with CSU versus control subjects, and 2 of 3 patients (67.9%) had sexual dysfunction. Impaired sexual functioning was linked to high disease activity and poor disease control. Sexual dysfunction was more common in patients with CSU with angioedema and vice versa. Angioedema was a significant predictor of sexual dysfunction in female patients with CSU (odds ratio, 7.3). Reduced sexual functioning was associated with anxiety, depression, and fatigue and significantly linked to impaired quality of life, more so in patients with angioedema as compared with those without. CONCLUSIONS: CSU has strong negative effects on female sexual function, especially in patients with angioedema. Additional studies on sexual health in patients with CSU are needed and should focus on the impact of effective treatment on sexual functioning.

Biologics for psoriasis: What is new?

Etiology of psoriasis is unclear but environmental, genetic, and immune factors act significant roles in the pathogenesis of this disease. Helper T cells (TH), plasmoid, and dermal dendritic cells play a prominent role in the development of classical psoriatic lesions. Interleukin stimulation is another important process in the pathogenesis of the disease that directly influences keratinocytes and leading to the formation of psoriatic pattern in the skin. Tumor necrosis factor (TNF) α which releases from keratinocytes activates dendritic cells in the early stages of complex pathogenesis of psoriasis. Activated keratinocytes also produce other proinflammatory cytokines (IL-1b and IL-6), antimicrobial peptides, and various chemokines. TNF activates dendritic cells that produce IL-23, leading to TH17 differentiation. TH17 cells secrete IL-17A, which has been shown to promote psoriatic skin changes. Consequently, after clarification of these main pathological mechanisms, anti-IL therapies have been accepted as a major treatment for patients with moderate-to-severe psoriasis. Here, actual information will be presented about biological agents currently in clinical use or being tested for clinical application for treatment of patients with psoriasis.

Does omalizumab treatment affect serum dehydroepiandrosterone sulphate levels in chronic idiopathic urticaria?

INTRODUCTION: It is known that serum dehydroepiandrosterone sulphate (DHEA-S) levels are low in patients with chronic idiopathic urticaria. AIM: In the study, the effect of the drug on the DHEA-S serum levels and its correlation with the remission and relapse times of the disease was investigated. MATERIAL AND METHODS: Fifty-seven patients with chronic idiopathic urticaria who were referred to our hospital and 20 healthy volunteers were included in the study. A subcutaneous injection of 300 mg omalizumab was administered to the patient group. Drug injections at this dose were completed (6 injections in total, one per month). Relations between serum DHEA-S levels and relapse rates, treatment response and remission duration of the patients and control group were investigated in the groups. RESULTS: Median DHEA-S value before treatment was 116.3 (21.5-448.7) µg/dl; the median DHEA-S value measured after 3 months was 98.4 (10.0-410.0) µg/dl (p = 0.003). The median DHEA-S value before treatment was 123.1 (21.5-299.6) µg/dl when the initial and 3-month DHEA-S levels of the 34 complete remission patients were compared; after 3 months the value was 100.4 (23.1-301.9) µg/dl (p = 0.021). CONCLUSIONS: This is the first study to investigate the effect of omalizumab treatment on DHEA-S levels in the treatment of chronic urticaria according to our literature review. The DHEA-S levels were found to be significantly lower after omalizumab therapy but not related to remission and relapse times.

The rapid effect of pulsed dye laser on demodex density of facial skin.

BACKGROUND: Recently, treatment with acaricides, which is aimed at reducing excessive proliferation of demodex mites, has gained popularity due to its providing a significant improvement in the symptoms of diseases, such as rosacea, seborrhoeic dermatitis, and perioral dermatitis. The effect of IPL on demodex mites was reported in skin biopsy specimens in three patients; however, to the best of our knowledge, no study exists to date, which evaluates the effect of pulsed dye laser (PDL) on demodex density (Dd) in larger patient group. We aim here in to observe the Dd before and after PDL therapy with two different skin biopsy techniques. MATERIAL AND METHODS: Thirty-one patients diagnosed with rosacea were included in the study who received PDL treatment. Dds which were measured by using both the SSSB (standardized skin surface biopsy) and CTM (cellophane tape method) techniques before and after 3 weeks of PDL therapy were evaluated. RESULTS AND DISCUSSION: The Dd of patients before PDL treatment was 13.0 (interquartile range (IQR): 5.0-28.0) and after 3 weeks of PDL treatment it was 6.0 (IQR: 3.0-12.0) with SSSB. After PDL treatment, the Dd was significantly lower than pretreatment the Dd (p = 0.002). The present study shows that PDL significantly reduced Dd in facial skin with one session.

Netherton syndrome previously misdiagnosed as hyper IgE syndrome caused by a probable mutation in SPINK5 C.

Özyurt K, Atasoy M, Ertas R, Ulas Y, Akkus MR, Kiraz A, Hennies HC. Netherton syndrome previously misdiagnosed as hyper IgE syndrome caused by a probable mutation in SPINK5 C. Turk J Pediatr 2019; 61: 604-607. Netherton syndrome (NS, MIM256500) is an autosomal recessive disorder that includes ichthyosis linearis circumflexa and a predisposition to allergies, asthma, and eczema, with hypereosinophilia, trichorrhexis invaginata, and elevated serum IgE levels. The genetic bases of Netherton syndrome are mutations in the gene SPINK5, and the Lymphoepitheial Kazal type related inhibitor, a serine protease inhibitor, is encoded by SPINK. Here a case is presented which showed a probable splice site mutation in SPINK5, which was previously unknown in databases and the literature, to point out the misdiagnosis of Hyper IgE Syndrome in the early presentation of the phenotype. This case highlights that a genetic test can be critical for identifying NS. The finding of underlying mutations contributes to the understanding of Netherton syndrome and is instrumental in indicating a specific therapy. Notably, treatment with acitretin has significantly improved both the ichthyosis linearis circumflexa and eczema in our patient.