Unveiling Treatment Response Predictors in Predominant Subtypes of Chronic Inducible Urticaria.

INTRODUCTION: Chronic inducible urticaria (CIndU) is a subtype of chronic urticaria (CU), which requires specific triggers to occur. Despite their common occurrence, treatment response rates and predictors of treatment responses are largely lacking in the literature. This study evaluates antihistamine (AH) and omalizumab response rates in the most common CIndU subtypes and examines whether certain features can predict treatment responses. METHODS: We retrospectively analyzed CU patients with at least one CIndU subtype and performed comparisons between subgroups, in a total of 423 patients (70% CIndU, 30% chronic spontaneous urticaria [CSU] plus CIndU). RESULTS: The treatment response rates in CIndU were 51.6%, 51.5%, and 86.5% with standard-dose second-generation H1-antihistamines (sgAHs), updosed/combined sgAH, and omalizumab, respectively. Overall AH response was higher in CIndU than CSU plus CIndU (78.3% vs. 62%, p = 0.002) and in symptomatic dermographism (SD) and cold urticaria (ColdU) than cholinergic urticaria (ChoU) (83.2% vs. 78.3 vs. 60.9%, p = 0.04). AH-refractory patients had a longer disease duration (45.2 ± 56.7 months vs. 37 ± 51.9 months, p = 0.04), more angioedema, accompanying CSU, mixed CIndU subtypes (37.5% vs. 21.1%, p = 0.003; 45.1% vs. 27.1%, p = 0.002; 8.8% vs. 2.4%, p = 0.014), and lower baseline urticaria control test scores (5.86 ± 3.3 vs. 8.6 ± 3.6, p < 0.001) than AH-responsive patients. CONCLUSION: CIndU exhibits a good response to both AHs and omalizumab. Notably, the response to AHs is more pronounced in SD and ColdU compared to ChoU. Disease duration, angioedema, accompanying CSU, mixed CIndU, and lower baseline UCT scores may be used to predict AH treatment outcome in CIndU.

Effect of Puberty, Menstruation, Pregnancy, Lactation, and Menopause on Chronic Urticaria Activity.

BACKGROUND: Chronic urticaria (CU) is a systemic disorder which is characterized by recurrent wheals and/or angioedema lasting more than 6 weeks. Sex hormones have been suggested to play a role in CU pathogenesis, however, their clinical implications have not been adequately described in the literature. OBJECTIVE: To determine whether conditions that change sex hormone levels such as puberty, menstruation, pregnancy, breastfeeding, and menopause affect the course of CU. METHODS: This cross-sectional questionnaire study was conducted on female CU patients at Okmeydani Training and Research Hospital UCARE Center between 2016 and 2017. The open-ended questionnaire consisted of questions evaluating the effects of hormonal changes on disease course. RESULTS: A total of 111 female CU patients were included in the analysis. During the perimenstrual period, CU symptoms worsened in 29% of patients but improved in 4.8%. The disease course did not change in the majority of patients during puberty, pregnancy, lactation, or menopause (100%, 96%, 83.8%, and 95.6%, respectively). CONCLUSIONS: Contrary to expectations, a change in sex hormone levels had no effect on the course of CU in the majority of cases. However, disease activity increased in one-third of CU patients during the perimenstrual period.

Differences between adult and pediatric chronic spontaneous urticaria from a cohort of 751 patients: Clinical features, associated conditions and indicators of treatment response.

BACKGROUND: Chronic spontaneous urticaria (CSU) is a common disease both in the pediatric and in the adult population. However, there are differences between the two patient populations with respect to etiological factors, comorbidities, and treatment responses. Our aim was to determine differences between pediatric and adult CSU in terms of clinical characteristics, laboratory parameters, comorbidities, response to treatment, and indicators of response. METHODS: A retrospective analysis of CSU patients was performed. Data regarding differences between pediatric and adult CSU patients were analyzed. Indicators of treatment response were determined separately in both pediatric and adult patients. RESULTS: Of 751 CSU patients (162 pediatrics and 589 adults), female dominancy (48.8% vs. 69.6%) and rate of angioedema (19.1% vs. 59.8%) were lower, and disease duration (5 months vs. 12 months) was shorter in pediatric patients. Anti-TPO positivity (24.7% vs. 9%), elevated CRP (46.5% vs. 11.1%), eosinopenia (38.5% vs. 18.1%), and skin prick test positivity (39.3% vs. 28.8%) were significantly more frequent in adult patients. Response to antihistamines was higher in the pediatric group, and only 7% used omalizumab versus 20.8% in the adults. The comparisons were also performed between <12-year and ≥12-year patients and yielded similar results. CONCLUSION: Pediatric CSU shows distinct characteristics such as lower incidence of angioedema and antithyroid antibodies, and it responds better to antihistamines. These suggest that CSU becomes more severe and refractory in adolescents and adults. Adolescent CSU shows features similar to adult CSU rather than pediatric CSU.

Assessment of disease activity and quality of life in patients with recurrent bradykinin-mediated versus mast cell-mediated angioedema.

OBJECTIVE: Recurrent Angioedema (RAE) is characterized by sudden swelling of mucosal surfaces or deep dermis and is either mast cell-(MMAE) or bradykinin-mediated (BMAE). How patients with BMAE and MMAE differ in terms of disease activity and impact remains largely unknown. Here, we determined validity, reliability, and sensitivity to change of Turkish versions of angioedema activity score (AAS) and quality of life questionnaire (AE-QoL) and used both instruments to investigate and compare patients with BMAE and MMAE. METHODS: Turkish versions of AAS28 and AE-QoL were applied to 94 patients with RAE (18-72 years). Patients' global self-assessment of QoL (PGA-QoL), disease activity (PGA-DA-VRS, PatGA-DA-VAS), and 12-Item-Short Form Survey were used at week 4 (visit 2), and week 8 (visit 3). Demographic characteristics, clinical features, and AAS28 and AE-QoL values were compared between 31 patients with BMAE and 63 patients with MMAE. RESULTS: Turkish AAS28 and AE-QoL showed excellent internal consistency, high reproducibility and known-groups validity. Compared to patients with MMAE, BMAE patients were younger (34.6 ± 10.7 vs. 40.7 ± 13.3 years), had longer disease duration (236 ± 178 vs. 51 ± 78 months), high prevalence of family history (63% vs 14%), longer duration of attacks (65 ± 20 vs. 40 ± 25 h), and they were more commonly affected by upper airway angioedema (70% vs 23%). Disease activity (AAS28) was lower (29.3 ± 24.6 vs 55.2 ± 52.9), but AE-QoL was higher (44.2 ± 16.1 vs 34.5 ± 22.5) in BMAE patients as compared to MMAE patients. CONCLUSIONS: Patients with BMAE and MMAE have distinct disease characteristics. Recurrent bradykinin-mediated angioedema impacts quality of life more than mast cell-mediated angioedema. The discriminating characteristics of patients with BMAE and MMAE may help to improve the diagnosis and management of patients with RAE.

Validation of the Turkish version of the Urticaria Control Test: Correlation with other tools and comparison between spontaneous and inducible chronic urticaria.

BACKGROUND: The urticaria control test (UCT) is a questionnaire designed to determine if chronic urticaria (CU) is controlled or not and to aid therapeutic decision-making. It collects retrospective information about the symptoms and quality of life impairment over the last 4 weeks. The current study aimed to investigate the validity, reliability and sensitivity to change of the Turkish version of the UCT. We also evaluated its correlation with other tools and compared the UCT results of patients with chronic spontaneous urticaria (CSU) and patients with chronic inducible urticaria (CINDU). METHODS: Following forward/backward translation and cognitive debriefing, the Turkish version of the UCT was used in 81 CSU and 78 CINDU patients. Dermatology life quality index (DLQI), Chronic urticaria quality of life questionnaire (CU-Q2oL), urticaria activity score (UAS), patients' and physicians' global assessment visual analog scores and Likert scales were used at baseline and after four weeks to assess quality of life impairment, disease activity and disease control. Statistical analysis to determine the validity and reliability of the Turkish version of the UCT as well as comparison between CINDU and CSU patients were performed. RESULTS: Duration of disease was longer, disease control was poorer and severe complaints were more frequent in CINDU patients (duration of disease: 36.3 (24) ± 49.1 vs 31.5 (9) ± 67.9, p = .007, UCT baseline: 8.4 (8) ± 3.4 vs 10.4 (11) ± 3.9, p = .001 and patient's global assessment Likert scale severe complaints: 6 vs 15, p < .001, respectively). The UCT showed excellent internal consistency for CSU and a minimally acceptable consistency for CINDU (Cronbach's α 0.89 for CSU versus 0.68 for CINDU). It showed strong correlation with CU-Q2oL but a moderate correlation with DLQI (r = -0.649, P < .001 and r = -0.545, P < .001, respectively). It was able to discriminate between patients with different disease control and was sensitive to detect changes in the disease control in both groups. The minimally important difference of the UCT was found to be 3. CONCLUSIONS: The Turkish version of the UCT is a valid and reliable tool for the management of CU patients and can be used both in CSU and CINDU patients to determine if the treatment is sufficient and if disease activity and quality of life impairment are under control or not.

Omalizumab as a Succesfull Therapy in Normocomplementemic Urticarial Vasculitis: A Series of Four Patients and Review of the Literature.

Urticarial vasculitis is an eruption characterized by inflamed itchy or painful red papules or plaques that resemble urticaria but last longer than 24 hours and heal with residual pigmentation or purpura. Histopathologically, urticarial vasculitis presents as leukocytoclastic vasculitis with perivascular infiltrate and fibrin deposits. The treatment options are oral antihistamines, oral corticosteroids, dapsone, colchicine and hydroxychloroquine. We report four cases with normocomplementemic urticarial vasculitis who were treated with omalizumab and a brief review of the literature on the use of omalizumab in normocomplementemic urticarial vasculitis.

Fric Test Revisited: A Suggestion for a New Scoring System and Its Correlation with Urticaria Control Test and Dermatology Life Quality Index.

BACKGROUND: Fric test is a useful tool for the diagnosis and threshold testing for symptomatic dermographism. When threshold testing is not available, Urticaria Control Test (UCT) and Dermatology Life Quality Index (DLQI) might be used to assess disease control and quality of life (QoL) impairment, respectively. OBJECTIVES: In this study, we aimed to describe a new scoring system for the Fric test and evaluate the correlations of Fric scores with UCT, DLQI, and other disease activity assessment scores. METHOD: Provocation test with Fric Test 4.0 was performed in all patients at referral and at the 4th week. We considered a 4-grade rating score for Fric Test (0-4) [Total Fric Score (TFS)]. A positive response with all of the four pins suggested severe dermographism (TFS = 4), while a wheal with only the largest pin (4.5 mm) was considered as milder disease (TFS = 1). Treatment responses were evaluated with Fric Test 4.0, UCT, patient's global assessment of disease severity (PatGA-VAS), the physician's global assessment of disease control (PhyGA-VAS), and DLQI at baseline and at the 4th week of treatment. The correlations of TFS with UCT, DLQI, PatGA-VAS, PhyGA-VAS at baseline as well as the changes in the mean scores after treatment (week 4) were performed. RESULTS: The mean UCT and DLQI scores were 8.69 ± 3.40 and 7.88 ± 6.02 at the first visit. At the second visit, TFS decreased from a mean of 2.79 ± 1.68 to 1.91 ± 1.85 (p < 0.001), and UCT scores and PhyGA-VAS were increased (p < 0.001), while DLQI scores, PatGA-VAS, and pruritus scores decreased significantly (p = 0.002; p = 0.001; p = 0.012). There was a positive correlation between TFS and pruritus scores (r = 0.378) and DLQI scores (r = 0.392). TFS was found to have a negative correlation with UCT score (r = -0.283) and PhyGA-VAS (r = -0.347). CONCLUSIONS: This new Fric scoring system allows comparison with other tools and shows moderate correlations with most of the tools. Using disease-specific tools is recommended since they provide a subjective evaluation of disease severity, QoL impairment, and disease control.

Omalizumab Updosing for Better Disease Control in Chronic Spontaneous Urticaria Patients.

The recommended dose of omalizumab for the treatment of chronic spontaneous urticaria (CSU) is 300 mg every 4 weeks, but there is no recommendation for patients who do not benefit from this dose. Our aim is to present the experiences on the use of doses of omalizumab higher than those recommended for CSU patients and to propose a protocol for updosing. This was a retrospective analysis of patients treated with omalizumab for CSU from 2 urticaria centers in Istanbul and Barcelona. The weekly urticaria activity score and/or the Urticaria Control Test (UCT) were used to monitor response. In Barcelona, a stepwise updosing regimen was preferred (450 mg first, then increasing to 600 mg), while in Istanbul, direct updosing to 600 mg was chosen. In Istanbul, 81 (88%) patients were treated with 300 mg, while 11 (12%) received 600 mg of omalizumab. In Barcelona, 7 (8.8%), 45 (56.3%), 17 (21.3%), and 11 (13.8%) patients received 150, 300, 450, and 600 mg of omalizumab, respectively. Urticaria control was achieved in 82.6% of the patients with 300 mg and in 8.7% of the patients with 600 mg in Istanbul, while it was achieved with 150 mg in 10%, with 300 mg in 48.8%, with 450 mg in 16.3%, and with 600 mg in 6.3% of the patients in Barcelona. In total, 123 (71.5%) patients responded to 150-300 mg and 26 (15.1%) to 450-600 mg. When responders to 150-300 mg (n = 123) were compared with responders to 450-600 mg (n = 26), BMI was found to be higher, and pre-omalizumab UCT was found to be lower in patients receiving updosed omalizumab (p = 0.029). Baseline data of the patients, especially BMI and pre-oma UCT, might be useful to determine if the patient will require higher doses of omalizumab. We recommend a stepwise approach starting from 450 mg and then updosing to 600 mg in CSU patients who do not respond or partially respond to 300 mg of omalizumab after 3-6 months of treatment.

Management of chronic inducible urticaria according to the guidelines: A prospective controlled study.

BACKGROUND: The recommended treatment approach in chronic inducible urticarias (CIndU) is the same as that for chronic spontaneous urticaria (CSU). But there is a lack of controlled trials assessing efficacy of available treatment options. OBJECTIVE: We aimed to evaluate the efficacy of treatment algorithm recommended by the guidelines and comparison of treatment responses in CIndU vs CSU. METHODS: This prospective parallel group controlled study included 70 CIndU and 66 CSU patients. The same treatment algorithm recommended by the European Academy of Allergology and Clinical Immunology/Global Allergy and Asthma European Network/European Dermatology Forum/World Allergy Organization (EAACI/GA2LEN/EDF/WAO) was implemented to both CSU and CIndU patients. Treatment responses of the groups were evaluated with urticaria control test (UCT) and dermatology life quality questionnaire (DLQI) scores at the 0, 4, 8, 12 and 24th weeks for CIndU and 0, 4, 12 and 24 weeks for CSU. RESULTS: Fourteen patients (20,9%) with CIndU and 25 (37,9%) with CSU responded to standard doses of H1-AHs which was significantly higher in the CSU group (p=0,031, p<0,05). Patients with CIndU and CSU showed statistically similar responses to 2nd line treatments (combining or updosing AHs) (p=0,979; p>0,05). Twenty-seven (40,3%) of CIndU patients and 21 (31,8%) of CSU patients were diagnosed as AH-resistant urticaria. Omalizumab was administered to 15 CSU patients and 17 CIndU patients. Response rates to omalizumab were similar in both groups. Total response rates increased from 37,9% (n:25) to 68,2% (n:45) with the 2nd line treatments in CSU group while it increased from 20,9% (n:14) to 59,7% (n:40) in CIndU group. When omalizumab was introduced to AH-refractory cases as a 3rd line treatment, total response rates evaluated at the 12th week were 76,1% (n:51) in patients with CIndU and 83,3% (n:55) in CSU. Continuing omalizumab treatment for 24 weeks increased response rates in patients who were unresponsive at week 12. CONCLUSION: CIndU seem to be more resistant to standard doses of AHs and higher doses of AHs are required for the control of symptoms. The same guidelines for CSU may be implemented to patients with CIndU.