key: cord-0867861-8unf09hh authors: Erdem, Yasemin; Polat Ekinci, Algün; Altunay, Ilknur Kivanc; Sivaz, Onur; Inal, Sena; Gokalp, Mehmet Onur; Pehlivan, Gizem; Özkaya, Esen title: The impact of COVID‐19 pandemic on the management of patients with chronic urticaria: An observational two‐center study from Turkey date: 2020-12-19 journal: Dermatol Ther DOI: 10.1111/dth.14652 sha: e8a2208bbff793f21dd5d9e3210b597ce1afbcbf doc_id: 867861 cord_uid: 8unf09hh The Coronavirus Disease 2019 (COVID‐19) outbreak significantly affected the clinical practice in hospitals and the management of many diseases. The aim of this study was to evaluate the effect of pandemic‐related factors on the severity and course of chronic urticaria (CU). A total of 194 CU patients who were on regular follow‐up, were enrolled in the study. The disease activity was assessed by means of the weekly urticaria activity score (UAS7) and urticaria control test (UCT). Patients were divided into two subgroups according to their disease aggravation as “aggravated” and “non‐aggravated”. Two groups were compared in terms of demographic, clinical, COVID‐19‐associated parameters, and parameters related with the effect of COVID‐19 pandemic on CU management. The omalizumab use was statistically higher (P = .017), and the systemic corticosteroid use was statistically lower (P = .025) in the “aggravated” group. Adherence to quarantine was significantly lower in the “aggravated” group (P = .027). 173 patients (89.2%) were unable to contact a dermatologist during the pandemic. Among 186 patients who received treatment for CU before the pandemic, 48 (25.8%) did not continue the existing treatment during the pandemic. CU aggravated in one patient with COVID‐19 and remained stable in the other. This study showed that CU patients, especially those on omalizumab therapy, had difficulties in attending medical care and even in the maintenance of their existing therapies during the pandemic. Creating novel follow‐up and treatment models as well as the increased use of teledermatology might be beneficial in the management of this life‐disturbing condition. hospitals were declared as pandemic hospitals. Elective procedures have been postponed, and outpatient services were closed. As a result, patients' access to health care centers was decreased, and the follow-up and treatment of chronic diseases became a problem. Chronic urticaria (CU) is one of the common skin diseases which is characterized by wheals, angioedema, or both, for more than 6 weeks. 2 The disease is of idiopathic nature in most of the cases, although infections, stress, drugs, and other factors might play a role in the etiology. Treatment is usually initiated with systemic antihistamines in standard or high dose, and continued with the addition of leukotriene antagonists, or alternative drugs such as doxepin, or omalizumab in unresponsive cases, according to treatment algorithms. [2] [3] [4] During the extraordinary pandemic conditions, procedures for the disease follow-up, management, and treatment have been updated, and guidelines have been published. [5] [6] [7] [8] [9] The aim of this study was to evaluate the effect of pandemic-related factors on the severity and course of the disease in a series of patients with CU. This prospective, observational study was conducted on 194 patients with CU in the allergy units of two dermatology departments. Systemic diseases including malignancies, focal and systemic infections, and food and drugs as triggering factors were ruled out. Patients with regular follow-up within the last year were enrolled in the study, excluding those with chronic inducible urticaria only. Detailed demographic (gender, age, marital status) and clinical (presence of concomitant disease, accompanying angioedema, duration of urticaria, drugs used for the treatment of urticaria, disease activity) parameters were recorded. Each patient was asked questions that were indicated in Table 2 , for the evaluation of the effects of the pandemic on the disease. The disease activity was assessed by means of the weekly urticaria activity score (UAS7) and urticaria control test (UCT). 10, 11 Both were evaluated before (before March 11, 2020) and during the pandemic (after June 1, 2020). The rationale on determining these dates was based on the report of the first case of COVID-19 on March 11, 2020, and the onset of a "new normalization" on June 1, 2020 in Turkey. 12 After the first case of COVID-19 was reported in Turkey on March 11, 2020, several hospitals have been turned to pandemic centers, whereas non-emergency routine health services and outpatient clinics stopped working. As of 1 June, according to a "new normalization" process, the outpatient clinics were opened, and the routine health services restarted. The "disease aggravation" was defined using the UAS7 score. Accordingly, a UAS7 score ≤ 6 before the pandemic and a UAS7 score ≥ 7 during the pandemic, and a minimum increase in UAS7 by 7 points during the pandemic was accepted as "aggravated" disease. Patients were divided into two subgroups according to their disease aggravation as "aggravated" and "non-aggravated". The above-mentioned demographic and clinical parameters were compared between these two groups. Furthermore, these two groups were compared in terms of COVID-19 associated parameters listed in Table 2 (the working status UAS7 score ranges reflect different levels of disease activity, that is, symptom free (0 points), minimal (1-6 points), mild (7-15 points), moderate (16-27 points) , and severe (28-42 points). 10 The UCT consists of four questions that are rated between 0 and 4 points. The total UCT score is calculated by summing up the points for all questions and ranges between 0 and 16. Low points indicate high disease activity and poor disease control. Scores between 0 and 11 were defined as "poor disease control", scores ≥12 as "good disease control". 11 The study was approved by the local ethics committee at the Şişli Hamidiye Etfal Training and Research Hospital (approval number: 2020/1618) and conducted in accordance with the Declaration of Helsinki. Statistical analyses were performed using SPSS software version 15 (SPSS Inc., Chicago, Illinois, USA). The descriptive statistics comprised the mean, SD, minimum and maximum scores for the numerical variables, and numbers and percentages for the categorical variables. The comparison of the independent variables in both groups was performed using the Student t test when there was a normal distribution and the Mann-Whitney U test when there was no normal distribution. The comparison was performed using the Kruskal-Wallis test when there were more than two groups. This study consisted of overall 194 CU patients including 133 (68.6%) females and 61 (31.4%) males. The male: female ratio was 1:2.2. The median age was 40 years (age range: 10-76 years). There was no statistically significant difference between patients with "aggravated" and "non-aggravated" disease regarding the demographic and clinical parameters with an exception of the drugs used for the treatment of CU ( Table 1 ). The omalizumab use was statistically higher (P < .05) and the systemic corticosteroid use was statistically lower (P < .05) in the "aggravated" group in comparison to the "non-aggravated" group (Table 1) . Although statistically not significant, the combined use of antihistamine and montelukast was more common in the "aggravated" group. The share of antihistamine use was similar in both groups. Table 2 shows a detailed comparison of COVID-19-associated parameters and the parameters related with the effect of COVID-19 pandemic on CU management between the "aggravated" and the "non-aggravated" groups. Adherence to quarantine was significantly lower in the "aggravated" group (P < .05). Although statistically not significant, the presence of COVID-19-like symptoms was more frequently associated with CU aggravation. Other parameters were similar between the two groups. Table 3 shows a detailed comparison of parameters related with the effect of COVID-19 pandemic on the two groups. Among 186 patients who received treatment for CU before the pandemic, 48 (25.8%) did not continue the existing treatment during the pandemic, and this was statistically similar between the "aggravated" and the "non-aggravated" groups. 173 patients (89.2%) were unable to contact their own or any other dermatologist during the pandemic (Table 3) . Table 4 shows a detailed evaluation of the disease severity. The mean UAS7 was 7.5 ± 10.2 before the pandemic, and 8.5 ± 11.2 during the pandemic ( Table 4 ). The difference was statistically not significant. The mean UCT score during the pandemic was found as 11.0 ± 3.7. Two patients (1%) were diagnosed with COVID-19. The clinical features of these patients were summarized in Table 5 . There were some differences between the "aggravated" and "non-aggravated" groups in this study. Interestingly, the use of omalizumab was significantly higher in the "aggravated" group. Omalizumab, as a novel treatment option, is known to be an effective and safe agent in the treatment of moderate to severe CU that is Of 194 patients 186 were receiving therapy for CU before the pandemic. b Patients expressed more than one reason to explain why they were unable to contact a dermatologist. Note: Categorical variables were compared using chi square test. T A B L E 2 The comparison of pandemic-related factors between two groups of patients with chronic urticaria Recently, it was recommended by study groups to continue omalizumab as home treatment during the pandemic. 8, 9 The main concern on the administration of omalizumab at home is the risk of anaphylaxis, however, this risk was reported to be very low (0.1%) in asthma bronchiale patients who received omalizumab. 16 On the other hand, CU patients receiving omalizumab treatment, were not reported to have anaphylaxis in the pivotal study, and only several suspicious cases of anaphylaxis were reported. 17 In the light of these data, administration of omalizumab at home in appropriate patients with CU was reported as safe, and home treatment was recommended after the fourth administration. 17 Postponing the appointments for non-urgent examinations, extending the intervals between the appointments, and increased use of teledermatology would be other preventive measures against the spread of the COVID-19 in and from hospitals. Teledermatology comes to the forefront as a preferable method in the pandemic period to protect both patients and physicians. 18 The use of systemic corticosteroids was significantly lower in the "aggravated" group. Systemic corticosteroids are fast acting and highly effective in urticaria. However, they are only recommended for short-term use to suppress the urticaria attacks in those with a poor response to antihistamines, in order to avoid long-term side effects. In this series, the higher use of systemic corticosteroids in the "nonaggravated" group seems to be related with a rapid symptom control, thus preventing disease aggravation. situations, as well as the preference of teledermatology or phone triage rather than face-to-face visits. 5, 6, 8 Further recommendations included avoidance of the triggering factors and learning of the stress coping methods. The benefit/risk ratio should be considered for each patient to select an appropriate treatment, especially for those whose treatment will be initiated at the pandemic-era. Non-sedative H1-antihistamines with their good efficacy and reliability profile, 2 are usually the preferred treatment of choice. There is no evidence that omalizumab has an immunosuppressant effect. Randomized controlled studies showed that omalizumab did not increase the risk of infection in the study group when compared with the placebo group. 26 Moreover, omalizumab was shown to promote the induction of interferon-α (IFN-α) production in plasmacytoid dendritic cells by IgE blockage, thereby reducing the susceptibility to viral respiratory tract infections. 27 Indeed, it was reported that omalizumab significantly reduced seasonal viral respiratory infections in children with asthma. 28 In light of these data, discontinuation of omalizumab was not recommended in patients who were already using this drug at the time when the pandemic started. 8 For patients with a definite diagnosis of COVID-19, on the other hand, it was recommended to discontinue any immunosuppressant therapies, whereas glucocorticoids should be tapered off. 8 There is no clear data on the use of omalizumab in COVID-19-positive patients. In a recent case report, omalizumab was initiated for a CU patient who had COVID-19 disease. 13 There are limited number of reports on the course of CU in patients with COVID-19 in the literature. 13 One patient was reported to have exacerbation of CU following the diagnosis of COVID- 19. 13 Two patients in our study group were diagnosed with COVID-19 disease. Exacerbation of urticaria was observed following the diagnosis of COVID-19 infection in one patient, whereas the severity of urticaria did not change in the other patient. Like other viral infections, COVID-19 might also be expected to cause exacerbations of CU. However, there might be several other triggering factors of CU such as drugs, or even psychogenic stress. Drugs for COVID-19 treatment such as chloroquine, hydroxychloroquine, lopinavir/ritonavir and other antiretroviral agents, and intravenous immunoglobulin treatment were reported to cause urticaria as well. 34 All these factors need to be considered when evaluating patients with exacerbations of CU during COVID-19 disease. The major limitation of this study was its small cohort size. However, the cohort consisted of registered CU patients who were on regular follow-up, which allowed us to provide data on their prepandemic clinical situation. This might be regarded as a strong aspect of this study. This study showed that CU was significantly aggravated in patients who were on omalizumab therapy. Patients had less access to health care services, leading to impaired maintenance of omalizumab therapy as the major negative impact of the pandemic on CU. Creating novel follow-up and treatment models as well as the increased use of teledermatology might be beneficial in the management of this lifedisturbing condition. WHO (2020) Considerations in adjusting public health and social measures in the context of COVID-19 (Interim Guidance The EAACI/GA 2 LEN/EDF/ WAO guideline for the definition, classification, diagnosis and management of urticaria The diagnosis and management of acute and chronic urticaria: 2014 update Doxepin in difficult-to-treat chronic urticaria: a retrospective, cross-sectional study from Turkey Management of allergic patients during the COVID-19 pandemic in Asia COVID-19: pandemic contingency planning for the allergy and immunology clinic Considerations on biologicals for patients with allergic disease in times of the COVID-19 pandemic: an EAACI statement Recommendations on the use of systemic treatments for urticaria and atopic dermatitis during the COVID-19 pandemic: Statement of Dermatoallergy Working Group of the Turkish Society of Modifications for adult allergy services during Covid-19 pandemic Comparison of urticaria activity score over 7 days (UAS7) values obtained from once-daily and twice-daily versions: results from the ASSURE-CSU study Chronic urticaria: tools to aid the diagnosis and assessment of disease status in daily practice COVID-19 Normalleşme Süreci ve Alınacak Tedbirler Chronic spontaneous urticaria exacerbation in a patient with COVID-19: rapid and excellent response to omalizumab Natural course of new-onset urticaria: results of a 10-year follow-up, nationwide, population-based study Omalizumab for the treatment of chronic idiopathic or spontaneous urticaria Summary of Product Characteristics: Xolair ® , Novartis Pharmaceuticals UK Ltd Home self-administration of omalizumab for chronic spontaneous urticaria Teledermatology in the wake of COVID-19: advantages and challenges to continued care in a time of disarray Management of urticaria in COVID-19 patients: a systematic review Pathophysiology, transmission, diagnosis, and treatment of Coronavirus Disease 2019 (COVID-19): a review Chronic urticaria and infections The effect of the "stay-at-home" policy on requests for dermatology outpatient clinic visits after the COVID-19 outbreak Dermatologists and SARS-CoV-2: the impact of the pandemic on daily practice Secure-AD and PsoProtect study groups. Global reporting of cases of COVID-19 in psoriasis and atopic dermatitis: an opportunity to inform care during a pandemic Treatment considerations for patients with pemphigus during the COVID-19 pandemic Omalizumab for the treatment of chronic spontaneous urticaria: a meta-analysis of randomized clinical trials What the physicians should know about mast cells, dendritic cells, urticaria, and omalizumab during COVID-19 or asymptomatic infections due to SARS-CoV-2? Randomized trial of omalizumab (anti-IgE) for asthma in inner-city children COVID-19 in a patient with severe asthma treated with Omalizumab Cutaneous manifestations of SARS CoV 2 infection: a clinical update The spectrum of COVID-19-associated dermatologic manifestations: an international registry of 716 patients from 31 countries Urticarial eruption in COVID-19 infection A case of COVID-19 pneumonia presenting with acute urticaria How to cite this article: Erdem Y, Polat Ekinci A, Altunay IK, et al. The impact of COVID-19 pandemic on the management of patients with chronic urticaria: An observational two-center study from Turkey The authors declare no potential conflict of interest.