Search

BackgroundThe appearance of bite cells associated with methemoglobinemia can be caused by oxidizing drugs such as dapsone in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency or high drug serum levels. Bite cells are often pathognomonic for oxidant injury in patients with G6PD deficiency and suggest active hemolysis.Case presentationWe report a case of a woman with no prior history of G6PD deficiency who presented with anemia, methemoglobinemia and bite cells on peripheral blood smear after dapsone therapy for new onset idiopathic urticaria. Laboratory tests for G6PD, blood count and liver function were within normal limits prior to initiation of therapy. During the patient's hospital course, moderate methemoglobinemia and anemia were identified despite mildly increased serum G6PD level. These pathologies were reversed upon stopping dapsone therapy.ConclusionThis case highlights the potential for therapeutic levels of dapsone to induce side effects in patients without G6PD deficiency and highlights the importance of routine blood monitoring for anemia and hemolysis during the course of drug therapy.

Ayurvedic therapies and practices have been integrated in universal wellness. Changes in lifestyle with development are very drastic. Diseased environment, junk food habits, work in shift duties, anxiety etc. are the main causative factors for vitiation ofTridoshaand the demonstration of diseases in today’s era. There is dearth of information aboutDincharyaandRitucharyain common people. Due to which people mainly get aggravated doshas related to their gastrointestinal system first, and then other symptoms come subsequently. According to Ayurveda Sheetpitta is described asTridoshaj Vyadhi(Disease), but Vata and Pitta Dosha are predominant and Ras and Rakta are main Dushya. Sheetapitta is one among theTwak Vikara(skin disorders) that have related Hetu of Kotha and Udarda. Vata and Kapha are two “Doshas”, which are primarily bothered which in turn is associated through Pitta resulting inTridosha Prakopacausing to redness, swelling itching on the skin etc. Chief symptoms of Sheetpitta are reddish spots, inflammation on skin with moderate to severe itching at site. It is compared with urticaria in modern science and termed as primary cutaneous disorder. An episode of it may start with pruritis. Episodes of urticaria may continue to revert for days, weeks, months or year if not cured properly. Urticaria is calculated as allergic reaction due to certain food and have only symptomatic treatment and anti-allergic drug. Commonly antihistaminic medicines were used for urticaria. In Ayurveda, treatment of Sheepitta includes Shodhana andShamana Chikitsa. Here we discussed about a case study of Sheetpitta. where we give Ayurvedic treatment and results were found very encouraging.

Chronic spontaneous urticaria (CSU) is a debilitating skin disease characterized by intensely itchy wheals, angioedema, or both. Symptoms recur spontaneously, on a near-daily basis, over >6 weeks; many patients experience flare-ups over several years and, consequently, reduced quality of life. Differences between the inflammatory profiles of the skin of CSU patients (wheals and nonlesional sites) and healthy controls indicate that key drivers such as mast cells, eosinophils, and basophils interact, release vasoactive mediators, and prime the skin, leaving patients predisposed to symptoms. Many cytokines and chemokines involved in these inflammatory networks and their corresponding intracellular signaling cascades have been identified. These insights informed the development of therapies such as omalizumab, dupilumab, and Bruton's tyrosine kinase (BTK) inhibitors, marking a renewed focus on pathogenesis in CSU clinical research. Despite progress, current therapies provide symptomatic control but do not appear to redress the inflammatory balance in the skin permanently. A deeper understanding of CSU pathogenesis will permit a more targeted approach to developing novel treatments with curative intent. Here, we review what is known about the pathogenesis of CSU and consider how this can be used to identify rational targets to improve patient care further.

Treatment of chronic spontaneous urticaria (CSU) is responsive to H1 antihistamines administered up to four times the recommended US Food and Drug Administration dose in approximately 50% of patients. However, when patients do not respond to these first-line agents, evidence-based guidelines using Grading of Recommendations, Assessment, Development, and Evaluations methodology have provided direction for second- and third-line treatments that can effectively treat patients with CSU. Some patients remain refractory to these advanced treatments; therefore, alternative treatments with a lower certainty of evidence may be necessary. Regardless of the therapies used to treat CSU patients, it is essential for clinicians to be knowledgeable about the mechanism of action, efficacy, and safety and monitoring recommendations of the treatments prescribed. This review provides a comprehensive review of the adverse effects and monitoring recommendations for agents in use for CSU treatment as well as those currently undergoing investigation for CSU treatment.

Chronic inducible urticaria (CIndU) is a subset of chronic urticaria that has an identifiable trigger. We present a case of postural urticaria induced by change in position in a 14-year-old girl. The patient’s CIndU was not adequately managed with both antihistamine and omalizumab treatment, indicating a recalcitrant form of CIndU.

Introduction: Drug allergies are often self-reported but of unknown accuracy. We carried out a prospective study to examine the utility and safety of formal allergology evaluation, and to identify factors associated with accurate drug allergy labels. Method: All patients who underwent drug allergy evaluation in our clinic during the study period were recruited. Baseline demographics, characteristics of index hypersensitivity reaction and outcomes of evaluation were recorded. Results: A total of 331 patients from March 2019 to June 2021 completed drug allergy evaluation to index drugs of concern. There were 123 (37%) male patients, and the mean age was 49 years (standard deviation 17). There were 170 beta-lactam antibiotics, 53 peri-operative drugs, 43 others, 38 non-steroidal anti-inflammatory drugs, and 27 non-beta-lactam antibiotic evaluations. Index reaction occurred within 5 years in 165 (50%) patients, with latency of less than 4 hours in 125 (38%) patients. The most common index reactions were rash, angioedema and urticaria. There were 57 (17%) evaluations stratified as low risk, 222 (67%) moderate risk, and 52 (16%) high risk based on multidisciplinary consensus. Allergy label was found to be false (negative drug evaluation) in 248 (75%) patients, while 16/237 (7%) skin tests, 44/331 (13%) in-clinic graded challenge, and 23/134 (17%) home prolonged challenges were positive (true drug allergy). The most common evaluation reactions were rash and urticaria. No cases of anaphylaxis were elicited. Conclusion: Seventy-five percent of drug allergy labels are inaccurate. Risk-stratified, protocolised allergy evaluation is safe. Prolonged drug challenge increases the sensitivity of drug allergy evaluation and should therefore be performed when indicated. Keywords: Drug allergy, drug hypersensitivity, graded challenge, prolonged drug provocation, skin testing

Coronavirus 2 is an infectious agent primarily identified as the cause of a pandemic viral pneumonia. With the mass vaccination against this virus, one of the health issues is the safety of currently available vaccines considering their adverse reactions. This systematic review was conducted to assess and summarize all reported data on histopathologic findings associated with mucocutaneous reactions that developed after COVID-19 vaccination for a better pathophysiology interpretation and clinical management of these reactions. A systematic search was performed in PubMed, Web of Science, and Scopus databases as well as Google Scholar engine for relevant English articles published till July 1, 2022. This review includes 131 studies with a total number of 287 cases. Eruptions that underwent a biopsy were mostly described as erythematous maculopapular, papulosquamous, vasculitis-like, lichenoid, or urticarial lesions. Histopathology revealed spongiosis, interstitial, and perivascular lymphohistiocytic infiltration, erythrocyte extravasation, parakeratosis, endothelial inflammation, and the like. Findings were highly consistent with morbilliform erythema, psoriasiform dermatosis, leukocytoclastic vasculitis, and lichenoid or urticarial drug reactions. The majority of these reactions had a mild nature and were primarily observed in patients with underlying health conditions. Microscopic evaluation was also consistent with transient inflammatory changes, and features like neutrophilic infiltrates, subcorneal pustules, and vasculopathy were less frequently reported than what seen in COVID infection. Therefore, dermatologic reactions developing after vaccination in the general population should not hinder a complete vaccination.

COVID-19 is a highly contagious respiratory tract infection caused by severe acute respiratory syndrome coronavirus 2. COVID-19 outbreak, which caused thousands of deaths, has been declared a pandemic by the World Health Organization in March 2020.Skin manifestations related to SARS-CoV-2 infection can be divided mainly into five groups: chilblainlike lesions (CBLLs), maculopapular eruptions, urticarial eruptions, vesicular eruptions, and livedo or necrosis. Other skin findings reported are erythema multiforme (EM)-like lesions and skin findings associated with multisystem inflammatory syndrome in children (MIS-C) and rarely with multisystem inflammatory syndrome in adults (MIS-A). Other manifestations such as pityriasis rosea or shingles are also reported.A total of 60 articles including reviews, studies and case reports were selected for the evaluation in this review.The skin manifestations associated with COVID-19 infection are numerous and can vary widely. The major dermatological patterns of COVID-19 can be classified as inflammatory reactions (maculopapular/morbilliform, urticarial and vesicular rashes), or lesions of vascular origin (chilblain like rashes, petechiae/purpura, and livedo acemose-like pattern) CONCLUSION: We believe that the dermatologist could play an important role in the response to the SARS-CoV-2 pandemic through early recognition of skin lesions suggestive of COVID-19, particularly in paucisymptomatic infections where this recognition could direct toward an early diagnosis of infection that certainly leads to a better prognosis.

Background: The European Network for Drug Allergy (ENDA) proposed a consensus document for hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) in 2011. A subgroup of patients with NSAIDs-exacerbated respiratory disease (NERD) develop urticaria/ angioedema type reactions in response to NSAIDs. The Kalyoncu classification might be a novel option to classify patients with NSAID hypersensitivity (NH). In this study, we compare the ENDA and the Kalyoncu classifications. Methods: This study enrolled a total of 196 patients. NH reaction types were categorized as asthma, rhinitis, urticaria/angioedema and anaphylaxis. Based on the reaction history and oral provocation test findings, patients were grouped according to ENDA and Kalyoncu classifications. Results: The mean age of the 196 patients was 40.32±13.28 years, and 130 (66.3%) of them were female. Under the ENDA and Kalyoncu classifications, the most common NH subgroups were NERD (32%), and isolated NH (34.2%), the least prevalent NH subgroups were single NSAID-induced delayed reactions (SNIDR) (1.5%), and pseudo Samter’s syndrome (11.7%). Conclusions: Our research revealed that the Kalyoncu classification is more descriptive of patients with NERD exhibiting urticaria/angioedema-type reactions. It also provides future risk assessment for development of NERD. For controversial cases, the Kalyoncu classification can be utilized as a new complimentary option alone or in conjunction with ENDA classification.

Introduction: Ibuprofen is the most common culprit drug causing nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity in children. We aimed to evaluate the frequency, clinical characteristics, and risk factors of confirmed ibuprofen allergy in children presenting with a history of suspected immediate type ibuprofen-induced hypersensitivity reactions. Methods: We evaluated 50 (35 M, 15 F) children with a median age of 7 years, who were referred to our clinic with suspected immediate ibuprofen hypersensitivity. Patients were subjected to a diagnostic work up including drug provocation tests (DPTs) with the culprit drug. Reactions were classified according to the European Academy of Allergy and Clinical Immunology Task Force recommendations for pediatric patients. Proven ibuprofen allergic patients underwent DPT to find a safe alternative drug. Results: Ibuprofen allergy was confirmed in 34% (n: 17) of children; 9 patients were diagnosed by DPTs and 8 patients diagnosed based on their histories. Angioedema was the most common clinical manifestation (n: 30, 60%). Among patients with proven ibuprofen allergy, 7 of them were classified as cross-intolerant. Cross-intolerance reactions were further classified as NSAID-exacerbated cutaneous disease (n = 1) and NSAID-induced urticaria/angioedema/anaphylaxis (n = 6). As an alternative drug, paracetamol was safely tolerated, whereas 1 patient developed angioedema and urticaria with nimesulide. Older age and male gender were identified as independent risk factors for immediate-type ibuprofen allergy. Conclusion: DPTs should be performed to confirm or exclude ibuprofen allergy in children and to find safe alternative drugs. Male gender and older age are risk factors for ibuprofen allergy. NSAID-induced hypersensitivity reactions in the pediatric population cannot be well defined using the adult classification system.

Urticaria following the COVID-19 vaccine was rarely reported and had a short self-limited resolution. However, there has been relatively little literature published on CSU induced by COVID-19 vaccines.We describe a case series of patients who experienced CSU after SARS-CoV-2 vaccination.A retrospective case series of 10 patients referred to the Department of Clinical Pharmacology of the University of Monastir (January 2021-January 2022) and included for evaluation of urticaria after COVID-19 vaccination.The median age was 31 years and patients were mostly female. Atopy was presented in 3 patients and urticaria was accompanied by angioedema in 6 patients. The median time interval between vaccination and the onset of urticaria was 28.5 h. The offended dose was the first one in 8 patients. The resolution of the eruption was observed at least 2 months later, despite the regular use of a full dose of antihistamine in nine patients. Polynuclear leucocytosis was identified in 5 patients. Anti-TPOAb was positive in one patient after receiving the BNT162b2 vaccine. Total serum IgE was elevated in 4 patients. Skin tests for the suspected vaccine as well as the vaccine excipient were negative.We add to the medical literature ten new cases of chronic spontaneous urticarial reactions following COVID-19 vaccines uncontrolled with high-dose first-generation H1 antihistamines.

The differential diagnosis of rashes in children is challenging. Pediatric rashes indicate a broad spectrum of clinical conditions and include those that are benign and self-limiting to those that may indicate a serious multisystem inflammatory response. It is essential that emergency nurse practitioners have the knowledge and skill set to accurately identify the spectrum of rashes in the pediatric population to arrive at the correct diagnosis for patient management and avoid costly and unnecessary diagnostic testing. The purpose of this article is to describe a case report of a young child with urticaria multiforme, a commonly misdiagnosed clinical condition, including the distinctive clinical features, differential diagnosis, and most current treatment recommendations. Other clinical conditions that present with skin lesions resembling urticaria multiforme conditions have also been discussed.

To assess the incidence and course of COVID-19 in patients with severe asthma/chronic spontaneous urticaria using biological agents.A total of 202 patients (142 with asthma, and 60 with urticaria) were enrolled. The subjects were asked via face-to-face or telephone interview whether they had been diagnosed with COVID-19 and the course of the disease.Study group consisted of 132 women, and 70 men (median age= 48 years). Median omalizumab dose was 300 mg/month in asthma (min-max= 150-1200 mg). The mepolizumab dose of two patients diagnosed with EGPA was 300 mg/month. Thirty one (15.3%) patients were diagnosed with COVID-19, 22 (71%) of whom were receiving omalizumab and nine (29%) were receiving mepolizumab. Asthma or chronic spontaneous urticaria diagnosis, age, sex, smoking, weight, comorbidities, atopy, and biological agent use were not statistically different between patients with or without COVID-19. Nine COVID-19 patients were hospitalized, and three of them required intensive care. Mepolizumab usage was higher in hospitalized patients (5, 55.6%), whereas omalizumab usage was higher in home-treated patients (18, 81%). The mean duration of biological use in home-treated patients was significantly higher than that of the hospitalized patients (35.64 months vs. 22.56 months, p= 0.024). Biological treatment was interrupted in 47 (23%) patients, selfinterruption due to the infection risk was the foremost reason (34%).The incidence of COVID-19 among patients with asthma and urticaria on mepolizumab and omalizumab was higher compared to studies from other countries. The disease course appeared mild in patients receiving long-term biological therapy.

Varied cutaneous manifestations of COVID-19 have been described, but most studies are based on photographic or application-based observations, without a direct observed-based evaluation by dermatologists.To study the types of cutaneous manifestations of COVID-19 among confirmed inpatients admitted to COVID-19 wards and intensive care units (ICUs).This cross-sectional analysis was conducted at a referral hospital in Delhi, India. Four hundred forty consecutive reverse transcription-polymerase chain reaction (RT-PCR)-confirmed cases diagnosed with moderate or severe COVID-19 and admitted to COVID-19 wards or ICUs, respectively, were included. A cutaneous finding was considered to be associated with COVID-19 if it had been described earlier as a consequence of COVID-19 and was observed at the time of or within the first 48 hours of admission (after excluding drugs and comorbidities as causes).Two hundred seventy patients with moderate COVID-19 were admitted to COVID-19 wards, whereas 170 with severe disease were admitted to ICUs. Only 7 of the 270 ward patients (2.59%) and 3 of the 170 ICU patients (1.76%) had cutaneous findings associated with COVID-19.Cutaneous findings attributable to COVID-19 are infrequent, and we believe that these might have been overestimated or overemphasized in earlier studies. Although coagulopathic findings may be associated with severe COVID-19, causation cannot be established in this cross-sectional study.

Background: chronic Spontaneous Urticaria (CSU) is characterized by recurrent wheals and/or angioedema for longer than 6-weeks. Guidelines recommend Omalizumab (Oma) as first-line and Cyclosporine-A (Cs-A) as second-line treatment in antihistamine resistant CSU. This step-wise algorithm might be time-consuming and costly. Objective: to determine indicators of response to Oma or Cs-A in CSU patients. Methods: we retrospectively analyzed data from seven centers in Turkey; the inclusion criteria for patients were to receive both Oma and Cs-A treatment (not concurrently) at some point in time during their follow-up. Clinical and laboratory features were compared between groups. Results: among 110 CSU patients; 47 (42.7%) were Oma-responders, 15 (13.6%) were Cs-A-responders, and 24 (21.8%) were both Oma and Cs-A responders and 24 (21.8%) were non-responders to either drug. High CRP levels were more frequent in Cs-A-responders (72.7% vs. 40.3%; p = 0.055). Oma-responders had higher baseline UCT (Urticaria Control Test) scores (6 vs. 4.5; p = 0.045). Responders to both drugs had less angioedema and higher baseline UCT scores compared to other groups (33.3% vs. 62.8%; p = 0.01 and 8 vs. 5; p = 0.017). Non-responders to both drugs had an increased frequency in the female gender and lower baseline UCT scores compared to other groups (87.5% vs. 61.6%; p = 0.017 and 5 vs. 7; p = 0.06). Study Limitations: retrospective nature, limited number of patients, no control group, the lack of the basophil activation (BAT) or BHRA (basophil histamine release assay) tests. Conclusions: baseline disease activity assessment, which considers the presence of angioedema and disease activity scores, gender, and CRP levels might be helpful to predict treatment outcomes in CSU patients and to choose the right treatment for each patient. Categorizing patients into particular endotypes could provide treatment optimization and increase treatment success., NA

Chronic spontaneous urticaria (CSU) is characterized by recurring wheals that last 6 weeks or longer without an identifiable cause. The estimated point prevalence of CSU worldwide is 1%. Furthermore, it has a significant impact on quality of life in both adults and pediatric patients and their families. Although it is most often a self-limited disease, some patients have urticaria refractory to first-line treatment: second-generation H1 antihistamines. In these patients, the use of targeted monoclonal antibodies is necessary. While omalizumab is the only Food and Drug Administration-approved monoclonal antibody for CSU, others, including ligelizumab, dupilumab, benralizumab, and several orally administered Bruton's tyrosine kinase inhibitors, are also promising therapeutics for reducing the morbidity of CSU. Novel therapies, among others discussed here, are rapidly being developed with new trials and therapeutics being released nearly monthly. Thus, we performed a scoping literature review of randomized controlled trials studying targeted therapies for CSU. We also discuss the pathophysiology, diagnosis, prognosis, and future research directions in CSU.

The prevalence of urticaria has been reported mostly in Europe and North America. However, precise information regarding its subtypes and clinical characteristics in primary care practice, especially in Asian countries, are scant. Patients with urticaria and/or angioedema who visited nine primary clinics of accredited dermatologists and allergologists in Japan were recruited from October to November 2020. The information of age, sex, disease duration, urticaria control test (UCT), and concomitant urticaria subtypes were collected. A total of 1061 patients participated. The number of patients was high in the 20 to 50 age groups with a peak in the 40s. The most frequent urticaria subtype was chronic spontaneous urticaria (CSU) followed by dermographism, acute spontaneous urticaria (ASU), angioedema, and cholinergic urticaria (CholU) (66.8%, 22.7%, 18.9%, 14.1% and 5.7% in all patients with urticaria). CSU development increased with age from the 20s to 50s, especially in females. Dermographism had a peak in the 40s. ASU had bimodal peaks in childhood and in the 30s. CholU was common in males in the 10-20s. Most angioedema patients were female with an increase in their 30s. Angioedema was solely present in 14 of 1061 participants (1.3%), while 136 (12.8%) had angioedema concomitant with urticaria. UCT showed poorly controlled urticaria with lower scores in patients with concomitant CSU and other subtypes than in those with CSU alone. Urticaria tends to develop in young to middle-aged females. The most common urticaria subtype is CSU, while the number of patients with CholU is high and that of angioedema is low in Japan.

Chronic urticaria (CU) appears with daily or intermittent/recurrent wheals with/without angioedema for more than six weeks. When no specific eliciting factors are found, chronic urticaria is defined as spontaneous (CSU). Up to 50% of patients with CSU do not respond to therapy, leading to a prolonged disease course and the need for expensive therapies, impacting the quality of life (QoL) and healthcare resources.Diagnosis of CSU is made when other potential causes of chronic urticaria are excluded. CSU therapy aims to achieve complete control of symptoms and normalization of QoL. Current treatment options for urticaria aim to target mast cell mediators such as histamine, or activators, such as autoantibodies. Guidelines recommend starting with second generation antihistamines (sgAHs) and adding omalizumab therapy if symptoms are not controlled. This review aims to provide a practical guide for CSU in the pediatric population.Treatment options for pediatric CSU are primarily based on adult data that have been extrapolated for children. Current guidelines should be reevaluated based on pediatric data, new biological treatments, and the COVID-19 pandemic. Future research is needed to investigate strategies to personalize current treatments and identify potential predictive biomarkers.

Tingling dermal pain triggered by sweating impairs the lives of patients with cholinergic urticaria and generalized anhidrosis. However, dermal pain evoked by sweating stimuli has been under investigated.To clarify characteristics of tingling dermal pain on sweating, we retrospectively evaluated clinical and histopathological manifestations in 30 patients having the main problem of dermal pain on sweating, and the efficacy of treatments.Dermal pain upon sweating affected mostly young males. It accompanied eruptions upon sweating and/or hypohidrosis in 24 patients, while 6 patients had dermal pain independently of hypohidrosis or eruptions. Dermal pain appeared immediately upon exposure to sweating stimuli, and disappeared within mostly 30 or 10 min. Hypohidrosis was not necessarily generalized but localized or absent. Histological analysis revealed that dermal pain could occur even without morphological changes and inflammation of sweat glands. Hypersensitivity to sweat contents was found only in 26% of patients. Sweat histamine and increase of plasma histamine after thermal induction in patients were significantly higher than those in healthy subjects. Effectiveness of steroid pulse therapy was demonstrated for dermal pain with hypohidrosis. Medications acting on nervous systems and regular sweat-inducing activities for promoting perspiration were also effective.Short-lasting tingling dermal pain appears immediately upon exposure to sweating stimuli, regardless of developing eruptions and/or presence of hypohidrosis, but possibly in association with sweat and plasma histamine.

Objective: During its first year, the AWARE study assessed disease activity, patient quality of life (QOL), and treatment patterns in chronic urticaria (CU) refractory to H1-antihistamines (H1-AH) in clinical practice. Methods: We performed an observational, prospective (24 months), international, multicenter study. The inclusion criteria were age ≥18 years and H1-AH–refractory CU (>2 months). At each visit, patients completed questionnaires to assess disease burden (Urticaria Control Test [UCT]), disease activity (7 day-Urticaria Activity Score [UAS7]), and QOL (Dermatology Life Quality index [DLQI], Chronic Urticaria Quality of Life Questionnaire [CU-Q2oL], and Angioedema Quality of Life Questionnaire [AE-QoL]). We present data for Spain. Results: The study population comprised 270 evaluable patients (73.3% female, mean [SD] age, 48.9 [14.7] years). At baseline, 89.3% were prescribed a CU treatment. After 1 year, first- and second-line treatments became less frequent and third-line treatments became more frequent. At baseline, 47.0% of patients experienced angioedema; at 1 year, this percentage had fallen to 11.8%. The mean (SD) AE-QoL score decreased from 45.2 (28.7) to 24.0 (25.8). The mean (SD) UCT score decreased from 7.0 (4.5) to 12.1 (4.1). According to UAS7, 38.2% of patients reported absence of wheals and itch in the previous 7 days at 1 year compared with 8.3% at baseline. The mean (SD) DLQI score decreased from 8.0 (7.4) to 2.8 (4.6). At the 1-year visit, the percentage of patients reporting a high or very high impact on QOL fell from 29.9% to 9.6%. Conclusions: H1-AH–refractory CU in Spain is characterized by absence of symptoms and a considerable impact on QOL. Continuous follow-up of CU patients and third-line therapies reduce disease burden and improve patients’ QOL.

Urticaria diagnosis may be challenging in children since it can be triggered or related to numerous conditions. In this paper, we reviewed the main aspects regarding the diagnosis of urticaria in the pediatric population. Acute urticaria is often due to viral infections. However, other culprits, including foods, insect stings, drugs, contrast media, vaccination, latex, and medical diseases, may account for acute patterns. Laboratory tests and confirmatory allergy tests should be individualized and guided by history. Chronic urticaria (CU) is defined when hives and/or angioedema last for more than 6 weeks. The most common type of chronic urticaria in children is chronic spontaneous urticaria (CSU). Chronic inducible urticaria (CindU) is less common but is important to diagnose in order to manage appropriately and reduce the risk of severe reactions. Inducible forms in children are often diagnosed with specific provocation tests similar to the tests used in adults. Given that chronic urticaria could rarely be a presentation of vasculitis, systemic-onset juvenile idiopathic arthritis, or auto-inflammatory syndromes, it is important to rule out these conditions. It is crucial to differentiate cases of chronic urticaria from mastocytosis and Bradykinin-mediated angioedema, given that treatment may differ. The management of chronic urticaria in children has improved over the last decade because of the development of both clear management guidelines and new effective drugs. It is crucial to increase awareness for appropriate diagnosis and new available treatment to improve the management of chronic urticaria in children.

Antihistamines, especially H1 antihistamines, are widely used in the treatment of allergic diseases such as urticaria and allergic rhinitis, mainly for reversing elevated histamine and anti-allergic effects. Antihistamines are generally safe, but some patients experience adverse reactions, such as cardiotoxicity, central inhibition and anticholinergic effects. There are also individual differences in antihistamine efficacy in clinical practice. The concept of individualized medicine has been deeply rooted in people's minds since it was put forward. Pharmacogenomics is the study of the role of inheritance in individual variations in drug response. In recent decades, pharmacogenomics has been developing rapidly, which provides new ideas for individualized medicine. Polymorphisms in the genes encoding metabolic enzymes, transporters and target receptors have been shown to affect the efficacy of antihistamines. In addition, recent evidence suggests that gene polymorphisms influence urticaria susceptibility and antihistamine therapy. Here, we summarize current reports in this area, aiming to contribute to future research in antihistamines and clinical guidance for antihistamines use in individualized medicine.

Shiitake mushrooms (This observational study is a retrospective review of cases in the French PCCs database between 1 January 2014 and 31 December 2019. Out of 125 shiitake exposures, we identified 59 cases of dermatitis: sex ratio of 1.80 M/F; ages ranging from 19 to 69 years (median: 39 years). Dermatitis occurred after raw or undercooked shiitake consumption (e.g., from the wok, in soup, or on pizza). The rash appeared 1-168 h (median: 48 h) after shiitake ingestion. Linear, erythematous, urticarial papules and plaques developed across the trunk, arms, and legs within a few hours and persisted for 1-40 d (median 10 d). The amount of shiitake eaten (lowThe mechanism of shiitake dermatitis is thought to involve lentinan, a heat-labile polysaccharide component. Inadequate cooking clearly seems to be a driver of the occurrence of shiitake dermatitis. This study highlighted a dose-dependent response, suggesting a partial toxic mechanism or a th1-type hypersensitivity mechanism. Treatment is focused on symptom management. Health professionals and the general population should be aware of both the risk associated with inadequately cooked shiitake consumption and the favourable prognosis of this still poorly known toxic dermatitis.

A urticária crónica (UC) é uma doença complexa, multifatorial, com diferentes fenótipos e endótipos, comum na prática clínica e que tem um impacto significativo na qualidade de vida do doente. O diagnóstico é essencialmente clínico. Os exames complementares podem contribuir para despistar fatores etiológicos/de agravamento e/ou comorbilidades, mas são escassos os biomarcadores de diagnóstico e/ou prognóstico e/ou resposta à terapêutica. Assim, na primeira consulta de um doente com UC, o Grupo Português de Estudos de Urticária (GPEU) propõe a realização de um interrogatório sistematizado, uniformizado e que permita identificar parâmetros associados a maior gravidade e que conduzam à otimização da terapêutica ou à orientação de exames complementares de diagnóstico.

Urticaria is a distressing dermatologic condition for many. Although the wheals of urticaria are characteristically evanescent, lasting less than 24 hours, patients tend to have recurrent episodes. Hives that last less than 6 weeks are considered acute urticaria. Acute urticaria does not routinely require supplementary work-up because the history often identifies a convincing, inciting allergen. Chronic urticaria is defined as episodes that occur for longer than 6 weeks, and there is often not an easily identifiable trigger. For both acute and chronic urticaria, patients frequently report food as a precipitating cause. For acute urticaria, the foods that are associated with true allergies, such as nuts and shellfish, are the most frequent offenders. The relationship between diet and chronic urticaria is not as firmly defined. Many patients unnecessarily restrict their diets, so it becomes the role of dermatologists to help patients identify if there is a reproducible link between their symptoms and their dietary exposures. The literature suggests that diets free from pseudoallergens and histamine-releasing foods may attenuate urticaria. Supplements such as fats, vitamin D, iron, and flavonoids have also been studied and may diminish symptoms.

Background: Allergic diseases represent a major global health issue with more than one-third of the global population affected by at least one allergic condition. Allergic conditions can not only cause life-threatening anaphylactic reactions but also impact daily life with a significant influence on mental health and the quality of life (QoL). Objectives: This study aims to evaluate the health-related QoL and depression severity among patients presenting in a tertiary care allergy center. Methods: A cross-sectional study was conducted among 596 patients presenting with allergic symptoms or previously diagnosed allergies between October 2018 and April 2019. Patients were screened for depression and the QoL impairment by using three validated scales: the Beck Depression Inventory (BDI), the Dermatologic Life Quality Index (DLQI), and the three-level version of the EuroQol 5-Dimensional (EQ-5D-3L) scale. Results: One-third (34.8%) of the study population was male and two-thirds (65.2%) were female. About 73.7% (n = 427/579) of the patients suffered from at least one previously diagnosed allergic disease, most frequently to pollen (37.0%, n = 214/579) and food (27.3%, n = 158/579), and 20.0 % (n = 116/579) suffered from urticaria. About 19.3% of the total population suffered from depression. Urticaria, as well as insect venom, food/food additives, and drug allergies significantly affected the QoL and depression severity (p < 0.001), reflected by higher DLQI and BDI scores, and lower scores in the EQ5D-3L index. Conclusion: Our results provide evidence for a possible correlation of allergies (e.g. against insect venom, food/food additives, and drugs) and/or urticaria with a reduced QoL and a higher depression rate. Patients particularly indicated restrictions for the dimensions, pain/discomfort as well as anxiety/depression. It might be beneficial to implement a standardized questionnaire as a regular screening method for evaluating the mental health status of patients with allergies and/or urticaria.

Introduction: Giardia intestinalis causes diarrhea and malabsorption, especially in developed countries. Although it primarily affects the gastrointestinal system, on rare occasions it causes allergic symptoms such as itching, urticaria, and eczema. Here we describe the case of a 19-year-old man with no past medical history who presented to our hospital with an atypical urticarial rash. Diagnosis: The only abnormal result in laboratory findings of stool parasitology was G. intestinalis. The patient was diagnosed with urticaria due to giardiasis. Intervention and outcomes: The patient was prescribed Bilastine tablet 20 mg 1 × 1 and referred to the Infectious Diseases Department for treatment. Co-Trimoxazole 400 mg/80 mg tablets 2 × 1 and Metronidazole 500 mg tablets 3 × 1 were prescribed. The urticaria had disappeared at the follow-up visit. The patient confirmed that urticarial symptoms did not recur. Conclusions: Despite their rarity, Giardia and other parasite infections can cause allergic symptoms. Parasitic factors should be considered in patients, especially those living in the communal areas, who present with treatment-resistant urticaria.

Background: Curcumin has been shown to decrease allergic symptoms and biomarkers in some animal and human studies. Objective: Our study aimed to determine if curcumin affects immediate skin-prick testing. Methods: We enrolled 34 participants sensitized to select antigens. The participants were randomized to treatment with curcumin or placebo in a double-blind fashion. The participants underwent titrated skin-prick testing before and after 1 week of treatment, and the pre- and posttreatment skin test wheals and flares were compared. Results: Curcumin did not have a statistically significant effect on immediate skin-prick test wheal or flare size. Conclusion: Although curcumin may attenuate allergic symptoms and biomarkers, it does not have a significant effect on immediate skin-prick test results and does not need to be discontinued before testing.

We report a case of occupational allergy to salmon combining allergic asthma, allergic rhinitis and allergic contact urticaria in a 59-year-old salmon-processing worker. Parvalbumin is the most common allergen, but indeed sensitisation to tropomyosin, preservatives and spices could occur.

Normocomplementemic urticarial vasculitis is a rare autoimmune disorder characterized by leukocytoclasia, fibrin deposits, and extravasated erythrocytes affecting multiple organ systems. Current treatment modalities, including corticosteroids and immunosuppressive agents, are of limited efficacy and an expansive side effect profile. Omalizumab has been reported to be effective in urticarial vasculitis, but its long-term effectiveness and tolerability have not yet been evaluated. We report a case of long-standing normocomplementemic urticarial vasculitis treated with omalizumab only, for almost 3 years. The patient reported a significant improvement in quality of life after the first few doses with a significant improvement in the urticaria control test. The treatment was well tolerated and no adverse events were reported after 3 years. Our patient was treated with 300 mg of omalizumab, as it was previously linked with a better improvement in quality of life. We were able to extend our patientrsquo;s treatment intervals, suggesting that this is feasible in patients treated with omalizumab who achieve a complete response. We recommend that larger and long-term studies are conducted to assess the efficacy and effectiveness of omalizumab in patients with urticarial vasculitis. J Drugs Dermatol. 2022;21(10):1124-1126. doi:10.36849/JDD.6739.

Introduction: This study aimed to evaluate factors affecting drug survival and treatment response in patients with chronic urticaria treated with omalizumab in clinical practice. Methods: This study included 386 patients with chronic urticaria. Demographic characteristics, clinical features, laboratory parameters, and omalizumab treatment data were analyzed retrospectively. The 7-day urticaria activity score (UAS7) and urticaria control test (UCT) were used to assess disease severity and treatment responses. Results: Well-controlled disease (UAS7 ≤6) was achieved in 59.3% of patients at a median of 2 months. Complete response was significantly higher in patients treated with omalizumab for ≥12 months (p < 0.001). Family history of asthma (p = 0.01) was less frequent, and disease duration (p = 0.041) was shorter in patients with well-controlled disease. Total treatment duration was longer in patients with relapse (p < 0.001) and serum Helicobacter pylori IgA positivity (p = 0.029). Discussion/Conclusion: Treatment response is better in patients treated with omalizumab for ≥12 months. However, prolonged treatment does not prevent relapse. Our findings suggest that continuous or intermittent therapy is an appropriate alternative treatment option in patients with severe chronic urticaria; however, continuous therapy can be preferred to maintain the patient’s quality of life.

Introduction: Chronic urticaria (CU) is a condition usually lasting longer than 6 weeks, with wheals and angioedema, sometimes both. Omalizumab is a recombinant humanized monoclonal IgG antibody developed against IgE. In some patients with CU, treatment response to omalizumab is good, but in some patients, it is poor. We aimed to compare the clinical features and laboratory parameters of the patients who responded and did not respond to omalizumab treatment among patients diagnosed with CU. Methods: Patients treated with omalizumab for the diagnosis of CU were evaluated retrospectively. Treatment response to omaliz­umab was evaluated by urticaria control test (UCT) (responder to omalizumab: UCT score ≥12 at 6 months and an increase of ≥3 compared to baseline). The clinical features and laboratory parameters of the patients who responded and did not respond to treatment were compared. Results: The mean age of the 220 patients, 66 (30%) men and 154 (70%) women, who received 300 mg of sc omalizumab every 4 weeks for CU was 38.89 ± 12.76 years. One hundred eighty-nine (85.9%) patients had good response to omalizumab treatment at the end of 6 months. Atopy (n = 73 [38.6%], p = 0.026), eosinophil count (median = 190 [0–800] [cells/µL], p < 0.001), basophil count (median = 40 [0–100] [cells/µL], p = 0.021), and total IgE (median = 240.5 [45–2,644] [kU/L], p < 0.001) level were significantly higher in the omalizumab responder patients (UCT score ≥12 at 6 months and an increase of ≥3 compared to baseline). Psychiatric disorders (n = 13 [41.9%], p = 0.008) and anti-TG (n = 11 [35.5%] [>2 IU/mL positive], p = 0.024) were significantly higher in the oma­lizumab nonresponder patients (UCT score ≤11 at 6 months). A weak but significant clinical correlation was found between blood eosinophil count (r = 0.168, p = 0.013), blood lymphocyte count (r = −0.149, p = 0.027), total IgE level (r = 0.207, p = 0.002), and increase in UCT score. As a result of the ROC curve analysis, the blood eosinophil count (AUC: 0.763, p < 0.001), total IgE level (AUC: 0.866, p < 0.001), and blood basophil count (AUC: 0.662, p = 0.004) had diagnostic value in predicting the response to omalizumab treatment in patients with CU. Conclusion: The patients with CU who were atopic with high eosinophils, high basophils, and high total IgE levels had good response to omalizumab treatment, but the patients with concomitant psychiatric disease and positive thyroid autoantibodies had poor response to omalizu­mab treatment. These findings obtained in our study should be tested in randomized controlled studies.

Background Natto (fermented soybeans)-induced hypersensitivity is characterized by delayed symptom onset that hampers diagnosis. We aimed to clarify the clinical utility of the basophil activation test (BAT) in the diagnosis of natto-induced hypersensitivity. Methods Five patients with a history of anaphylaxis and chronic urticaria suspected of natto-induced hypersensitivity and seven with chronic spontaneous urticaria clinically unrelated to natto were enrolled in the patient and control groups, respectively. The BAT was performed with two incubation times, 15 min and 1 h, in combination with various concentrations of natto-mucilage extract. Results In controls, CD203c levels in basophils remained low in the 15-min incubation but were significantly increased in the 1-h incubation. In the patient group, in the 15-min condition, basophil CD203c was significantly upregulated by natto mucilage but not by soybean vs controls (P = 0.001). Low concentrations of natto mucilage were sufficient to upregulate basophil CD203c in the anaphylaxis cases, but high concentrations were required to induce the same effect in the urticaria cases. Finally, the dose-dependent pattern of the BAT results differed significantly between the anaphylaxis and urticaria cases (P = 0.006). Thus, a strong background reaction was observed in the BAT with 1 h incubation; 15 min of incubation was sufficient to identify patients with natto-induced hypersensitivity and may distinguish the clinical phenotype of natto-induced hypersensitivity, i.e., anaphylaxis or urticaria. Conclusions The BAT with a 15-min incubation period is useful in diagnosing natto-induced hypersensitivity.

Resumen: Antecedentes: La urticaria crónica (UC) es una enfermedad debilitante cuyo tratamiento es principalmente sintomático. El estudio UCREX tuvo como objetivo identificar el perfil de los pacientes con UC, el manejo de la enfermedad y la calidad de vida (CdV) en la práctica clínica diaria en España. Métodos: Estudio observacional, prospectivo, multicéntrico de 12 meses, que incluyó pacientes con UC de novo o establecida que acudieron a la consulta de dermatología/alergología de 39 hospitales españoles. Las variables principales fueron: el Urticaria Activity Score (UAS) y el UAS por siete días (UAS7). Las variables secundarias fueron: el cuestionario de CdV de urticaria crónica (CU-Q2oL), el EuroQol-5 Dimensiones (EQ-5D), la escala Medical Outcomes Study Sleep (MOS-Sleep) y la escala hospitalaria de ansiedad y depresión (HADS). Resultados: Se incluyeron 361 pacientes, de los cuales 176 (48,8%) formaron parte del análisis del objetivo principal. La edad media (DE) fue de 46,6 (14,2) años y el 71,8% eran del sexo femenino. El año anterior al periodo de inclusión de los pacientes, la mayoría de ellos (57,1%) se habían tratado con antihistamínicos H1 no sedantes (AHNS-H1). En la basal, se registró una media (DE) de 3,6 (6,8) de visitas a atención primaria. La media (DE) del UAS7 en la basal fue de 14,3 (11,0) y del CU-Q2oL 24,1 (17,0), observándose una tendencia en la mejoría en 8,6 (9,7) y 13,9 (15,0), respectivamente, a los 12 meses. El MOS-Sleep y el EQ-5D se mantuvieron estables durante el estudio, excepto por el dolor/malestar y la ansiedad/depresión que pasaron de 58,7 y 49,6% a 29,6 y 26,9%, respectivamente. En situación basal, el HADS mostró una ansiedad media (DE) de 8,7 (4,5) y una depresión de 5,1 (4,4), disminuyendo respectivamente a 7,0 (4,3) y 4,7 (4,3) a los 12 meses. Conclusiones: Aunque la mayoría de los pacientes son tratados con AHNS-H1, la actividad de la enfermedad sigue siendo importante, afectando negativamente a su CdV, su actividad laboral y repercutiendo negativamente en el uso de recursos sanitarios. Un manejo adecuado de la enfermedad podría ser la base para alcanzar el control de los síntomas, la mejora de la CdV y la optimización de los recursos sanitarios necesarios. Abstract: Background: Chronic Urticaria (CU) is a debilitating disease whose treatment is mainly symptomatic. UCREX study aimed to identify CU patients’ profile, disease management and quality-of-life (QoL) in daily clinical practice in Spain. Methods: Observational, 12-months prospective, multicenter study, included de novo or established CU patients attending to dermatology/allergy consultations in 39 Spanish hospitals. Main variables: Urticaria Activity Score (UAS), UAS over 7 days (UAS7). Secondary variables: CU-QoL Questionnaire (CU-Q2oL), EuroQol-5 dimensions (EQ-5D), Medical Outcomes Study Sleep (MOS-Sleep) scale, Hospital Anxiety and Depression Scale (HADS). Results: 361 patients included. Of them, 176 (48.8%) considered for the main objective analysis. Mean age (SD) of 46.6 (14.2) years and 71.8% women. The year prior to inclusion, most patients (57.1%) were treated with non-sedating H1-antihistamines (NS-H1AH). At baseline, mean (SD) 3.6 (6.8) visits were registered to primary care. Mean (SD) UAS7 at baseline was 14.3 (11.0) and CU-Q2oL 24.1 (17.0) which tended to improve by 8.6 (9.7) and 13.9 (15.0), respectively, at 12-months. MOS-Sleep and EQ-5D remained steady during the study, except pain/discomfort and anxiety/depression which went from 58.7% and 49.6% to 29.6% and 26.9%, respectively. At baseline, HADS showed a mean (SD) anxiety of 8.7 (4.5) and depression 5.1 (4.4), decreasing to 7.0 (4.3) and 4.7 (4.3), respectively, at 12-months. Conclusions: Although most CU patients are treated with NS-H1AH, disease activity is still important, negatively affecting patients’ QoL, work activity and healthcare resources use. An appropriate disease management could be the basis for symptoms control, QoL improvement and resources optimization.

Management guidelines for allergic rhinitis and urticaria recommend oral second-generation antihistamines as first-line treatment. The efficacy and safety of bilastine, the newest nonsedating second-generation antihistamine, are well established in adolescents/adults with these allergic conditions. The bilastine development program for pediatric use (2–

Introduction: The aim of this study was to compare the pharmacodynamic activity of bilastine administered under fasting and fed conditions in healthy volunteers. Methods: In this randomized, open-label, two-period, crossover study involving 24 healthy subjects, once-daily oral bilastine 20 mg was administered for 4 days under fasting and fed conditions, with a 7-day washout period. Bilastine plasma concentrations were measured for 24 h after the first and fourth doses in each period. Pharmacodynamic activity was assessed by wheal and flare surface inhibition and subjective assessment of itching, after intradermal injection of histamine 5 μg. Results: When administered under fed versus fasting conditions, exposure to bilastine 20 mg decreased (mean maximum plasma concentration and area under the curve from time 0 to 24 h decreased by 34.27% and 32.72% [day 1], respectively, and 33.08% and 28.87% [day 4]). Despite this, the antihistaminic effect of bilastine 20 mg was not altered by food. On day 1, as assessed by wheal and flare surface inhibition, the maximum effect and duration of action of bilastine did not differ to a significant extent between fasting and fed conditions, with only a short 30-min delay in the onset of wheal inhibition. At steady state (day 4), bilastine’s pharmacodynamic effects were not significantly affected under fasting or fed conditions. Conclusion: The pharmacokinetic interaction of bilastine with food does not imply a significant reduction of its peripheral antihistaminic efficacy. Despite a slight delay in onset of action on the first treatment day, the global clinical efficacy of bilastine is not affected by coadministration with food.

Background: As the vaccination campaign in response to the coronavirus disease 2019 (COVID-19) pandemic continues, concerns with regard to adverse reactions to the vaccine remain. Although immediate hypersensitivity reactions have received much attention, delayed systemic urticarial reactions after vaccination can occur. Objective: To describe the clinical presentation, vaccine excipient skin testing results, and outcomes of subsequent COVID-19 vaccination in patients who experienced delayed systemic urticarial reactions after messenger RNA (mRNA) COVID-19 vaccination. Methods: This was a retrospective case series of 12 patients referred to the Mayo Clinics in Rochester, Minnesota, and Jacksonville, Florida, between January 19, 2021, and April 30, 2021, for evaluation of delayed systemic urticarial reactions after mRNA COVID-19 vaccination. Demographics, medical and allergic history, reaction details, vaccine excipient skin testing results (when performed), and the outcome after subsequent vaccination were collected for each patient. Results: The mean age of the patients was 52 years, all were white, and 9 (75%) were women. Half of the patients had a history of drug allergy, and one had a history of chronic spontaneous urticaria. Seven patients reacted to the Pfizer-BioNTech vaccine and five reacted to the Moderna vaccine. Seven patients developed symptoms between 8 and 24 hours after vaccination. Nine patients required antihistamines for treatment. The median time to symptom resolution was 4 days. Nine patients underwent allergist-directed COVID-19 vaccine excipient skin testing, all of which were negative. Ten patients chose to receive their next mRNA COVID-19 vaccine dose, and four patients experienced recurrent delayed urticaria. Conclusion: Delayed systemic urticarial reactions after mRNA COVID-19 vaccination were not life-threatening, could be treated with antihistamines, and were not predicted with vaccine excipient skin testing. They were not a contraindication to subsequent vaccination, although patients should be counseled with regard to the possibility of recurrence.

The infection caused by the recently identified SARS-CoV-2, dubbed coronavirus disease-19 (COVID-19), has become a pandemic. With exponential growth of morbidity among the people around the world, the clinical characteristics of COVID-19 are becoming clearer and description of new disease symptoms descriptions is emerging. The sufficient amount of descriptions of various skin manifestations in patients with COVID-19 has appeared, however they are characterized by great heterogeneity. The pathogenetic mechanisms of the development of skin rashes in patients with COVID-19 are currently unknown, however, hypotheses have been put forward that they have an overactive immune response, activation of the complement system and microvascular damage. Based on the published literature data and our own experience, the following characteristic types of skin rashes can be distinguished among the skin manifestations of this viral disease: urticaria, confluent, papulovesicular exanthema, acral rashes similar to frostbite, livedo reticularis and purpura. Possible development of skin lesions against the background of the development of COVID-19 provides the need to inform dermatologists about the features of the skin manifestations of this disease, as well as to study further these symptoms of COVID-19 to determine their diagnostic and prognostic value.

We report the case of a previously healthy 13-month-old boy who developed transient, annular and erythematous wheals with dusky centres affecting the face, trunk and limbs, associated with pruritus, non-pitting oedema of upper and lower extremities and dermographism ([figure 1][1]). The rash spared

PURPOSE. To evaluate the incidence of urticarial adverse drug reactions (ADRs) to ACE inhibitors and beta-blockers, patient demographics, drug causality, and treatment outcome. METHODS. An epidemiological study including 154 patients with urticarial ADRs, out of a total of 3554 hospitalized patients in the Clinic of Dermatology and Venereology, for a 7-year period. ADRs were defined according to the WHO and the Naranjo algorithm was used for case drug causality assessment. RESULTS. Urticarial ADRs were found in 4,1% of the study population (≥ 18 years), the average age was 50,2 years, and female prevalence was established. Concomitant cardiovascular diseases were found in 45,2% of the patients and 30,1% declared using ACE inhibitors and/or beta-blockers. The suspected drug was withdrawn, and alternative therapy was recommended by a cardiologist. The Naranjo algorithm showed 4.5% “definitive”, 45,5% “possible”, and 50% “probable” urticarial ADRs. Systemic antihistamines were administered to all patients and single short corticosteroid courses were added in 81,8%. Clinical recovery was achieved in 59% of the patients and improvement in 41%. CONCLUSIONS. The need for drug therapy and hospitalization in severe cases of urticarial ADRs to ACE inhibitors and beta-blockers are factors contributing to the overall socio-economic burden of ADRs.

Although favipiravir is a promising drug for coronavirus disease 2019, some adverse effects, including skin lesions, have been reported. A 56-year-old female who was prescribed favipiravir by a filiation team following a positive severe acute respiratory syndrome coronavirus 2 polymerase chain reaction test presented to our hospital. After examination, favipiravir and paracetamol were prescribed. She represented to the hospital with facial swelling and itchy rashes on her forearm. Angioedema and urticaria were diagnosed. Favipiravir was discontinued. Steroid and antihistaminic therapy were administered for angioedema. To our knowledge, this is the first reported case of favipiravir-induced angioedema and urticaria in Turkey.

This study aims to explore the effect of Jingfang Mixture on the protein expression of urticaria in mice and explain the mechanism of Jingfang Mixture in the treatment of urticaria. Twenty-seven male Kunming mice were randomly divided into a normal group, a model group and a Jingfang Mixture group according to body weight. Except for the normal group, mice in the model group and the Jingfang Mixture group were injected with the mixture of ovalbumin and Al(OH)_3 gel for the first immunization, and the second immunization was performed on the 10 th day to induce the urticaria model. Mice in the Jingfang Mixture group started to be administered on the 6 th day after the initial immunization, and was administered continuously for 21 days. The normal group and the model group were replaced with the same amount of purified water. Twenty-four hours after the last administration, an appropriate amount of skin was taken, and label-free quantitative proteomics technology was used to detect the differences in protein expression in skin tissue. The signaling pathways involved in the differential proteins was further analyzed. The results of proteomics indicated that seventy-six proteins were involved in the intervention of Jingfang Mixture on mice with urticaria, and the differential proteins were mainly enriched in biological process(BP), molecular function(MF), and cellular component(CC). Kyoto Encyclopedia of Genes and Genomes(KEGG) analysis showed that the signaling pathways regulated by Jingfang Mixture mainly involved carbon metabolism, metabolic pathways, glucagon signaling pathway, glycolysis/gluconeogenesis, pentose phosphate pathway, hypoxia inducible factor-1(HIF-1) signaling pathway, purine metabolism, adherens junction, calcium signaling pathway, leukocyte transendothelial migration, and inflammatory mediator regulation of transient receptor potential(TRP) channels, which were involved in skin tissue energy metabolism and immune regulation. The findings of this study showed that the protective effect of Jingfang Mixture on mice with urticaria was closely related to the regulation of immune disorders, and the regulatory effect on immune system may be achieved through the regulation of energy metabolism by Jingfang Mixture.