Newborn-onset chronic urticaria as the first manifestation of NLRP3 mosaicism

Objectives: A 7-month-old boy presented with generalized urticaria since the first week of life, without any other clinical manifestation. Cow's milk allergy was ruled out. His development was normal for his age. Maternal history was significant for COVID-19 infection in the third trimester of pregnancy with mild symptoms. Family history was significant for dermatographism in a maternal uncle. Hives were migratory with no single lesion persisting more than 24 h. There were no recognizable triggers and only relieved for 1-2 days after each vaccination. Patient was treated with optimal doses of antihistamines without improvement. Method(s): Laboratory tests and further studies were performed Results: Laboratory tests were normal including complete blood testing, circulating autoantibodies and infectious studies. C-reactive protein level and erythrocyte sedimentation rate were elevated. Due to chronic urticaria of newborn onset unresponsive to antihistamines a monogenic autoinflammatory disease was suspected. A targeted gene panel covering causative genes revealed the unreported p.Gly307Ala variant in the NLRP3 gene with a variant allele frequency (VAF) of 3% compatible with gene mosaicism. NLRP3 variant was classified as "likely pathogenic" based on its location, where a different variant has been reported as causing a severe form of cryopyrin-associated periodic syndromes (CAPS), and bioinformatic analyses. As expected, the variant was absent in patient's parents supporting for its de novo nature. Vision and hearing exams were normal. Treatment with canakinumab will start soon. Discussion(s): CAPS are dominantly-inherited autoinflammatory diseases caused by gain-of-function NLRP3 variants. These variants are often germline, but in some reported cases the variants are postzygotic causing gene mosaicism as in the patient here described. We believe that the mild presentation in our patient, despite having a likely pathogenic variant, may be explained by the low VAF. The genetic diagnosis in our patient allowed early initiation of anti-IL-1 treatment, which probably will prevent the development of other CAPS manifestations.

Characteristics of immune response profile in patients with immediate allergic and autoimmune urticarial reactions induced by SARS-CoV-2 vaccines.

Severe allergic reactions following SARS-COV-2 vaccination are generally rare, but the reactions are increasingly reported. Some patients may develop prolonged urticarial reactions following SARS-COV-2 vaccination. Herein, we investigated the risk factors and immune mechanisms for patients with SARS-COV-2 vaccines-induced immediate allergy and chronic urticaria (CU). We prospectively recruited and analyzed 129 patients with SARS-COV-2 vaccine-induced immediate allergic and urticarial reactions as well as 115 SARS-COV-2 vaccines-tolerant individuals from multiple medical centers during 2021-2022. The clinical manifestations included acute urticaria, anaphylaxis, and delayed to chronic urticaria developed after SARS-COV-2 vaccinations. The serum levels of histamine, IL-2, IL-4, IL-6, IL-8, IL-17 A, TARC, and PARC were significantly elevated in allergic patients comparing to tolerant subjects (P-values = 4.5 × 10-5-0.039). Ex vivo basophil revealed that basophils from allergic patients could be significantly activated by SARS-COV-2 vaccine excipients (polyethylene glycol 2000 and polysorbate 80) or spike protein (P-values from 3.5 × 10-4 to 0.043). Further BAT study stimulated by patients' autoserum showed positive in 81.3% of patients with CU induced by SARS-COV-2 vaccination (P = 4.2 × 10-13), and the reactions could be attenuated by anti-IgE antibody. Autoantibodies screening also identified the significantly increased of IgE-anti-IL-24, IgG-anti-FcεRI, IgG-anti-thyroid peroxidase (TPO), and IgG-anti-thyroid-related proteins in SARS-COV-2 vaccines-induced CU patients comparing to SARS-COV-2 vaccines-tolerant controls (P-values = 4.6 × 10-10-0.048). Some patients with SARS-COV-2 vaccines-induced recalcitrant CU patients could be successfully treated with anti-IgE therapy. In conclusion, our results revealed that multiple vaccine components, inflammatory cytokines, and autoreactive IgG/IgE antibodies contribute to SARS-COV-2 vaccine-induced immediate allergic and autoimmune urticarial reactions.

Outcomes of chronic spontaneous urticaria in a patient with non-Hodgkin's lymphoma and SARS-Cov- 2 infection: Efficacy of treatment with omalizumab

Case report Background: Association of chronic spontaneous urticaria (CSU) with malignancies and worsening of urticaria during COVID-19 have been reported. The efficacy of treatment of CSU with omalizumab in the context of malignancies or COVID-19 is not well established. Method(s): Case report of a patient followed for 9 years with CSU. Data collected from Medical Records and interviews during consultations. Result(s): Female, 29 years-old, came to clinic in 2013 for investigation, diagnosed with CSU. She also presented mild asthma, allergic rhinitis and history of urticaria after taking amoxicillin. She had a positive autologous serum skin test, and positive skin tests to dust mite, cat, cockroach, peanut and milk. Her total IgE was 227IU/ mL. Anti-nuclear and anti-thyroid antibodies were negative;ERS 13mm, blood eosinophils 300/mm3, and stool exam negative for parasites. She showed no response to second generation antihistamines up to fourfold doses, with UCT < 6 and CU-QoL = 89. After 6 months, omalizumab was added at 300 mg subcutaneously, every 4 weeks. The patient showed immediate reactions after the two applications of omalizumab: first, diffuse pruritus and throat tightness;second, worsening of urticaria and pruritus, requiring iv medications. Treatment with omalizumab was stopped, she was kept on fourfold dose of bilastine with partial control of symptoms. In 2016, she presented worsening of urticaria (UCT = 1), weight loss of 6kg/2 months, daily fever and enlarged cervical lymph nodes, and was diagnosed with diffuse large B-cell non-Hodgkin's lymphoma. Following chemotherapy with cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab, she presented complete resolution of urticaria. Two years after remission of the lymphoma, in 2019, she presented recurrence of urticaria, and treatment with fourfold dose of bilastine was reinitiated with control of symptoms (UCT = 16). Investigation ruled out recurrence of lymphoma. In May 2021, she was diagnosed with SARS-CoV- 2 infection. Symptoms of COVID-19 were runny nose and low grade fever, however urticaria got worse and no longer responsive to bilastine. Treatment with omalizumab was attempted, with no reactions and good efficacy after the first dose, with an UCT = 15, and urticaria remains controlled on treatment with omalizumab to present. Conclusion(s): In this report, we highlight the efficacy and safety of using omalizumab in a patient with refractory CSU associated with neoplasia and SARS-CoV- 2 infection.

Characteristics of immune response profile in patients with immediate allergic and autoimmune urticarial reactions induced by COVID-19 vaccines

Allergic and hypersensitivity reactions induced by COVID-19 vaccines are increasingly reported and some patients may develop prolonged urticarial reactions following COVID-19 vaccination. Herein, we investigated the risk factors and immune mechanisms for patients with COVID-19 vaccines-induced immediate allergy and chronic urticaria (CU). We prospectively recruited and analyzed 129 patients with COVID-19 vaccine-induced immediate allergic and urticarial reactions as well as 115 COVID-19 vaccines-tolerant individuals from multiple medical centers during 2021-2022. The clinical manifestations included acute urticaria, anaphylaxis, and delayed to chronic urticaria developed after COVID-19 vaccinations. The serum levels of histamine, IL-2, IL-4, IL-6, IL-8, IL-17A, TARC, and PARC were significantly elevated in allergic patients comparing to tolerant subjects (P-values=4.5x10-5-0.039). Ex vivo basophil revealed that basophils from allergic patients could be significantly activated by COVID-19 vaccine excipients (polyethylene glycol 2000 and polysorbate 80) or spike protein (P-values from 3.5x10-4 to 0.043). Further BAT study stimulated by patients' autoserum showed positive in 81.3% of patients with CU induced by COVID-19 vaccination (P=4.2x10-13), and the reactions could be attenuated by anti-IgE antibody. Autoantibodies screening also identified the significantly increased of IgE-anti-IL-24, IgG-anti-FceRI, IgG-anti-TPO, and IgG-anti-thyroid-related proteins in COVID-19 vaccines-induced CU patients comparing to SARS-COV-2 vaccines-tolerant controls (P-values= 4.6x10-10-0.048). Patients with COVID-19 vaccines-induced recalcitrant CU patients could be successfully treated with anti-IgE therapy. In conclusion, our results revealed that multiple vaccine components, inflammatory cytokines, and autoreactive IgG/IgE antibodies contribute to COVID-19 vaccine-induced immediate allergic and autoimmune urticarial reactions (Minor revision in Journal of Autoimmunity [IF=14.551]).Copyright © 2023

Omalizumab administration for refractory to H1-antihistamines chronic urticaria has a protective effect against symptomatic COVID-19 infection: Results from the GREEk National Urticaria Registry (GREENUR)

Background: There is no evidence clearly defining whether the administration of immunomodulatory biologic agents to allergic patients affects their immune response to COVID-19 infection. The current guidelines suggest the continuation of their use in patients who are not infected, while the continuation is individualized in the case of symptomatic disease. We sought to determine the cumulative incidence of symptomatic COVID-19 infection among chronic urticaria (CU) Greek patients, who, until 2/2/2021, were under omalizumab for at least two months. This was the date on which no Greek citizen was considered fully immunized due to vaccination against SARS-CoV- 2. Method(s): The present study extracted data from the first national multicenter registry of patients in Greece with chronic urticaria (GREEk National Urticaria Registry, GREENUR). All patients with CU under omalizumab during the pandemic, and the clinical characteristics of those with COVID-19 symptomatic infection, were recorded. Result(s): 329 patients were included (223 with CSU alone). Only 10/329 (6 women) or 3% had symptomatic COVID-19 infection confirmed by Polymerase Chain Reaction (PCR) analysis. Overall, 6 patients reported fever (up to 39.5degreeC), 5 rhinitis, 3 cough, one of which reported shortness of breath controlled with bronchodilation, 5 hyposmia/anosmia and ageusia, 8 muscle weakness, 5 arthralgia/ myalgia, and 7 headache. None of the patients was admitted to the hospital. According to the Centers for Disease Control and Prevention (CDC), only 1 in 4.2 cases of COVID-19 is being examined, of which 84% are symptomatic. Consequently, the cumulative incidence of symptomatic COVID-19 infection in the general Greek population on 2/2/2021 (number of confirmed cases on that date: 158,716) was estimated at 5.2%, significantly higher than that among patients with CU (p-value = 0.02). Conclusion(s): The cumulative incidence of symptomatic COVID-19 infection among patients with CU under omalizumab treatment is lower than that of the general population. All infected patients had a mild course and short duration of the disease and did not need hospitalization. These findings demonstrate not only the safety but also a protective role of omalizumab in patients with CU during the COVID-19 pandemic.

Vaccination of patients with chronic urticaria

Background: The importance of vaccination in today's world is extremely important given the COVID-19 epidemic. About 30% of the world's population suffers from allergies. Among them, 25% of patients according to the WHO, had an episode of urticaria at least once in their life. Urticaria is one of the most common allergic diseases, which is the highest in-patient admission toll at Dnipro Allergy Center. During the year 2021, 600 patients with urticaria were treated in the hospital. Patients with chronic recurrent urticaria do not want to be vaccinated because of the fear of complications such as anaphylaxis.Vaccination of urticaria patients without complications. Method(s): The study involved 45 patients aged 18 to 65 years, with a mean age of 34.3 +/- 1.0 (13 males and 32 females). The average experience of the disease is 3.6 +/- 0.8 years. Patients with chronic recurrent urticaria were admitted to the in-patient unit. Prior to vaccination, they were tested for tryptase levels, a detailed platelet blood test, coagulogram, D-dimer, and ECG. Result(s): Many patients had concominant gastrointestinal pathology in the form of gastro-esophageal reflux disease (GERD) -20 patients (44.4%), peptic ulcer disease disease -17 patients (37.7%), or stomach pathology in 45 patients (100%), which required proton pump inhibitors (PPI). Given that PPIs are a risk factor for anaphylaxis, according to EAACI documents, PPIs were discontinued three days before vaccination. Serum tryptase levels were elevated in 3 patients (13 mug/l, 16 mug/l, 32 mug/l). All patients underwent premedication. At normal serum tryptase levels, patients received 1-fold dose of desloratadine, and at high serum tryptase levels: 13 mug/l, 16 mug/l and 32 mug/l, patients received 4-fold dose of desloratadine. After 30 minutes vaccination shot was carried out without side effects and without complications of allergic nature. The second vaccination shot was also protected by antihistamines, so all the patients we observed had received 2 shots of the vaccine not complicated by side effects such as fever or allergic reactions. Conclusion(s): All patients were vaccinated without complications. In urticaria patients, serum tryptase levels should be determined prior to vaccination. Depending on the level of tryptase, appropriate premedication is prescribed: with a high level of tryptase -4- fold dose of desloratodine, with a normal level -1- fold dose. All patients with urticaria should be diagnosed with concomitant pathology in order to correct the basic therapy before vaccination.

New onset chronic spontaneous urticaria post COVID-19 vaccination in South Africa

Background: Chronic spontaneous urticaria (CSU) is a common chronic inflammatory disease. There have been small case series of new onset CSU post COVID-19 infection as well as reports of new onset CSU or worsening of existing CSU post COVID-19 vaccination. Dermatological side effects post COVID-19 vaccine are typically delayed, self-limiting urticaria. We have described the characteristics of patients who have developed new onset CSU post COVID-19 vaccination. Method(s): All patients referred to the UCT Lung Institute Allergy clinic from the initiation of the COVID-19 vaccine roll out (February 2021) were reviewed to identify patients that developed new onset CSU within 12 weeks of receiving a COVID-19 vaccine. Medical history, response to therapy, and available laboratory investigations were reviewed by clinic physicians. Result(s): We identified seven patients that developed CSU post COVID-19 vaccine. The median age of the cohort is 39 (IQR 32-45) and the majority are female (n = 5). The most common vaccine was the Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine (n = 6, 85.7%), and one patient received the Jansen Ad26.COV2.S vaccine. No patients had COVID-19 infection prior to vaccination and only one patient contracted COVID-19 post vaccination. The median time to the development of symptoms post vaccination was 14 days (IQR 2;44) and the median time to diagnosis was 90 days (IQR 45;120). Most patients (n = 4) reported angioedema and urticaria, one patient reported isolated angioedema, and two isolated urticaria. The median initial UAS7 score was 37.5 (IQR 24.5;46) and the initial CU-Q2oL score was 72 (IQR 56;76) indicating severe disease activity. All but one patient had a history of atopy with the most common diagnoses being allergic rhinitis (n = 5) and atopic dermatitis (n = 3). All patients had normal eosinophil counts and over half of the patients (n = 4) had an elevated total IgE level (median 26.4 [IQR 9.8;194]). All patients were HIV negative and one patient had positive Helicobacter pylori serology. All had normal serum protein electrophoresis, thyroid function (with negative thyroid autoantibodies), and negative antinuclear antibodies. All patients started on high dose antihistamine therapy with 71.1% having partial or no response to therapy. Conclusion(s): New onset CSU is a rare side effect of COVID-19 vaccination with poor response to high dose antihistamine therapy. It is important that allergists and physicians are aware of the possibility of new onset CSU post COVID-19 vaccine and further research is needed to identify risk factors.

Palmoplantar inflammation with a broad differential diagnosis made clear upon patch testing

A 51-year-old woman presented to our service with a 2-year history of severely painful, thickened skin of her bilateral hands and feet. She advised of considerable skin pain on mobilizing. She intermittently applied acrylate nails. This was on a background of chronic urticaria, asthma and allergic rhinitis. She described a positive family history of psoriasis. On examination, there was marked hyperkeratosis with welldemarcated erythema on the central palms and entire fingers with deep fissuring and scale. Similar finding were noted on the soles of the feet particularly affecting the heels, arch and also the tips of the toes. The morphology of the lesions favoured psoriasis, but the differential diagnosis included chronic hand dermatitis. She was referred for topical psoralen + ultraviolet A (PUVA) and patch testing to standard battery and acrylates. Treatment with topical PUVA was discontinued and patch testing lists were cancelled as a result of the emergence of COVID-19 in Ireland. Topical therapy of clobetasol propionate was initiated. On follow-up review, the appearances of her feet and hands had deteriorated significantly. She was commenced on acitretin 10 mg once daily, which was escalated to 20 mg 2 months later. Clinical improvement was noted, but appearances deteriorated once again following the application of acrylic nails. Further history revealed the patient had assisted with the application of acrylic nails to clients years prior to her initial review. Patch testing took place 18 months after initial review due to outpatient list cancellations secondary to the COVID-19 pandemic. Upon review 48 h after the application of the (METH) Acrylate Series, the patient was found to have a +2 reaction to 2- hydroxyethyl methacrylate and a further +2 reaction to 2- Hydroxypropyl methacrylate. At her 96-h review, both reaction sites were marked at +1. Following complete avoidance of acrylates, the palmoplantar inflammation entirely resolved. This case highlights the importance of a detailed clinical history where contact dermatitis is considered. In our patient's case, the clinical history and examination of the palmoplantar eruption combined with the first-degree family history of psoriasis were highly suggestive of a diagnosis of psoriasis. The episodic severe flares and its refractory nature to treatment raised suspicion for allergic contact dermatitis. Dermatologists should remain alert for potential contact allergens in cases of severe palmoplantar psoriasis. A further area for consideration is the deleterious effect the COVID-19 pandemic had on the successful diagnosis and treatment of dermatological patients through the cancellation of outpatient services.

New-Onset Chronic Spontaneous Urticaria Post Covid-19 Vaccination in South Africa

INTRODUCTION Chronic spontaneous urticaria (CSU) is a common chronic inflammatory disease. There have been small case series of new onset CSU post-COVID-19 infection and reports of new onset or worsening of existing CSU post COVID-19 vaccination. A dermatological side-effect post COVID-19 vaccine is typically delayed, self-limiting urticaria. We have described the characteristics of patients who have developed new-onset CSU post COVID-19 vaccination. METHOD All patients referred to the Allergy Clinic since the initiation of the COVID-19 vaccine roll-out in South Africa were reviewed to identify patients who had developed new-onset CSU within 12 weeks of receiving a COVID-19 vaccine. Medical history, response to therapy and available laboratory investigations were reviewed by clinic physicians. RESULTS We identified seven patients who developed CSU post COVID-19 vaccination. The median age of the cohort is 39 (IQR 32-45) and the majority are female (n = 5). The most common vaccine was the Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine (n = 6;85). The median time to the development of symptoms post-vaccination was 14 days (IQR 2;44) and the median time to diagnosis was 90 days (IQR 45;120). The median initial UAS7 score was 37.5 (IQR 24.5;46) and the initial CU-Q2oL score was 72 (IQR 56;76), which indicated severe disease activity. All but one patient had a history of atopy, with the most common diagnoses being allergic rhinitis (AR) (n = 5) and atopic dermatitis (AD) (n = 3). All the patients had normal eosinophil counts and more than half of the patients (n = 4) had an elevated total IgE level (median 26.4 [IQR 9.8;194]). All of the patients were HIV-negative. All of them had normal serum protein electrophoresis, thyroid function (with negative thyroid autoantibodies) and negative antinuclear antibodies. All of them started on high-dose antihistamine therapy, with 71.1% having partial or no response to the therapy. CONCLUSION New-onset CSU is a rare side-effect of COVID-19 vaccination, with poor response to high-dose antihistamine therapy. It is important that allergists and physicians are aware of the possibility of new-onset CSU post COVID-19 vaccination and further research is needed to identify any risk factors.

Immunopharmacology/Musculoskeletal System Pharmacology: Overview

The rapid technological advancement over the past few decades has profoundly influenced the scientific approaches that shape the therapeutic landscape. Undoubtedly, immunopharmacology is an important player in the modern era of transition toward precision medicine that is largely defined by the identification of patient-specific therapies. According to the Immunopharmacology Section - ImmuPhar of the International Union of Basic and Clinical Pharmacology (IUPHAR), immunopharmacology is considered to be the youngest area of pharmacology dealing with the selective modulation, mostly up- or down-regulation, of specific immune responses that are often accomplished by immune cell subsets with specialized functions. Although the recent biotechnological progress has made available new classes of drugs with improved selectivity and/or specificity, agents possessing immunomodulating activities have been used in clinical practice for more than 70years. A pertinent example from the late 1940s is the counteraction of the inflammatory response upon administration of cortisone in patients with rheumatoid arthritis. © 2022 Elsevier Inc. All rights reserved

Delayed-Onset Urticaria Following Vaccination for COVID-19

Background: As COVID-19 vaccines continue to be administered worldwide, there are an increasing number of studies documenting cutaneous reactions following vaccination. Systemic reactions, such as urticarial diseases, occur. Purpose(s): The main objective of this study was to investigate the association between urticaria and recent vaccination for COVID-19. Method(s): A retrospective chart review examining the association of urticaria and COVID vaccination was conducted. Result(s): We report 17 patients who developed an urticarial reaction following vaccination against COVID and one patient who developed an urticarial reaction following a COVID infection. The vast majority of the patients were women with a mean age of 42.8 years. Conclusion(s): Cutaneous manifestations often follow COVID vaccination and infection. It may be helpful to inquire about recent infections and vaccinations in patients presenting with urticarial diseases. Copyright © 2022 Journal of Dermatology and Dermatologic Surgery.

Delayed-Onset Urticaria Following Vaccination for COVID-19

Background: As COVID-19 vaccines continue to be administered worldwide, there are an increasing number of studies documenting cutaneous reactions following vaccination. Systemic reactions, such as urticarial diseases, occur. Purpose(s): The main objective of this study was to investigate the association between urticaria and recent vaccination for COVID-19. Method(s): A retrospective chart review examining the association of urticaria and COVID vaccination was conducted. Result(s): We report 17 patients who developed an urticarial reaction following vaccination against COVID and one patient who developed an urticarial reaction following a COVID infection. The vast majority of the patients were women with a mean age of 42.8 years. Conclusion(s): Cutaneous manifestations often follow COVID vaccination and infection. It may be helpful to inquire about recent infections and vaccinations in patients presenting with urticarial diseases. Copyright © 2022 Journal of Dermatology and Dermatologic Surgery.

Urticarial Vasculitis Masquerading as Typical Acute Urticaria

Introduction: Urticaria is a common condition which has clinical overlap with urticarial vasculitis, a rare entity affecting <1% of the population. We report a case of typical acute urticaria evolving into urticarial vasculitis. Case Description: A 58-year-old female with a history of endometrial hyperplasia, Hashimoto's thyroiditis, and asthma was initially seen in Allergy and Immunology clinic following an episode of severe perioperative anaphylaxis, determined to be due to cefazolin. Two months later, she presented with new-onset urticaria and angioedema following a mild self-resolving viral illness. The rash was pruritic, with migratory lesions lasting for <24 hours, and not associated with ecchymoses upon resolution. Initial physical examination was notable for erythematous wheals with blanching. She was started on high dose second-generation antihistamines and received multiple steroid tapers with transient improvement. Four weeks after initiation of the rash, she developed a new-onset burning sensation at its site and subsequently developed painful hyperpigmented purpuric lesions in prior areas of urticaria. She had no associated fever, ocular involvement, abdominal pain, or joint pains. Laboratory values were significant for negative CBC, CMP, ESR, TSH, tryptase, c-KIT mutation analysis, ANA, C1q, C3, C4, and SARS-CoV-2 nucleocapsid antibodies. Extensive autoimmune workup was negative. Skin biopsy revealed leukocytoclastic vasculitis consistent with urticarial vasculitis. Patient was started on omalizumab with initial improvement. Discussion(s): Although initially presenting with acute urticaria, the progression of atypical urticarial symptoms warranted consideration of alternative diagnoses, including urticarial vasculitis. This case highlights the clinical overlap between acute/chronic urticaria and urticarial vasculitis which may result in a delay in diagnosis. Copyright © 2022

Integrated bioinformatics to identify potential key biomarkers for COVID-19-related chronic urticaria.

Background: A lot of studies have revealed that chronic urticaria (CU) is closely linked with COVID-19. However, there is a lack of further study at the gene level. This research is aimed to investigate the molecular mechanism of COVID-19-related CU via bioinformatic ways. Methods: The RNA expression profile datasets of CU (GSE72540) and COVID-19 (GSE164805) were used for the training data and GSE57178 for the verification data. After recognizing the shared differently expressed genes (DEGs) of COVID-19 and CU, genes enrichment, WGCNA, PPI network, and immune infiltration analyses were performed. In addition, machine learning LASSO regression was employed to identify key genes from hub genes. Finally, the networks, gene-TF-miRNA-lncRNA, and drug-gene, of key genes were constructed, and RNA expression analysis was utilized for verification. Results: We recognized 322 shared DEGs, and the functional analyses displayed that they mainly participated in immunomodulation of COVID-19-related CU. 9 hub genes (CD86, FCGR3A, AIF1, CD163, CCL4, TNF, CYBB, MMP9, and CCL3) were explored through the WGCNA and PPI network. Moreover, FCGR3A, TNF, and CCL3 were further identified as key genes via LASSO regression analysis, and the ROC curves confirmed the dependability of their diagnostic value. Furthermore, our results showed that the key genes were significantly associated with the primary infiltration cells of CU and COVID-19, such as mast cells and macrophages M0. In addition, the key gene-TF-miRNA-lncRNA network was constructed, which contained 46 regulation axes. And most lncRNAs of the network were proved to be a significant expression in CU. Finally, the key gene-drug interaction network, including 84 possible therapeutical medicines, was developed, and their protein-protein docking might make this prediction more feasible. Conclusions: To sum up, FCGR3A, TNF, and CCL3 might be potential biomarkers for COVID-19-related CU, and the common pathways and related molecules we explored in this study might provide new ideas for further mechanistic research.

Unusual cutaneous leukocytoclastic vasculitis: A case report

Leukocytoclastic vasculitis, also known as cutaneous small vessel vasculitis, embodies a challenging condition for both the physician and the patient. This condition is affecting mainly the small vessels, commonly the post-capillary venules, being characterized by presence of neutrophilic infiltration within and throughout the vessel wall with signs of leukocytoclasia, fibrinoid necrosis and local damage to the vessel wall and the surrounding tissue. Frequently, it is associated with other conditions (cryoglobulinemic vasculitis, IgA vasculitis, ANCA-associated vasculitides), infections, medication, systemic diseases (systemic lupus erythematosus, Sjogren syndrome, rheumatoid arthritis). Cutaneous leukocytoclastic vasculitis is considered a rare condition. We are presenting a 46 year old man, with history of chronic urticaria, presented in our clinic for recurrent intensely pruritic urticarian plaques, disseminated on limbs and trunk, associating bullae with serocitrin content. Petechiae and palpable purpura were observed just in a few places. Bullous lesions occurred after the patient went through COVID-19 and followed a self-treatment with paracetamol. Patch and prick tests were performed on this patient, identifying positive reactions to hydroxyisohexyl-3-cyclohexane-carboxaldehyde, fragrance mix and paracetamol. Histopathological exam evidentiated tipically aspect for leukocytoclastic vasculitis and subepidermal vesicle-bullae lesion. IgM/IgG immune complexes, C3 and fibrinogen were found positive in direct immunofluorescence exam. Through this scientific paper, we are presenting the crucial role of direct immunofluorescence exam in early diagnosis and evolution of this condition, efficacy of oral therapy with dapsone (anti-inflammatory properties, antioxidant scavenger effect, inhibitory effect on chemotaxis and function of neutrophils). Copyright © 2022

Navigating patients with atopic dermatitis or chronic spontaneous urticaria during the COVID-19 pandemic.

A rapid spread of different strains of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to an unprecedented pandemic. Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, the medical body has encountered major obstacles concerning disease management at different levels. Even though patients infected with this virus mainly present with respiratory symptoms, it has been associated with a plethora of well-documented cutaneous manifestations in the literature. However, little investigations have been conducted concerning COVID-19 and its impact on skin disorders mediated by type 2 inflammation leaving multiple dermatologists and other specialists perplexed by the lack of clinical guidelines or pathways. This review focuses on the effects of this pandemic in patients with skin disorders mediated by type 2 inflammation, specifically atopic dermatitis and chronic spontaneous urticaria. In addition, it will provide clinicians a guide on treatment and vaccination considerations for this stated set of patients.

Use of teleconsultation by allergists: Results of the 2021 CNPA survey

Teleconsultation has been a reimbursed tool for monitoring patients since 2018 but which experienced a phenomenal boom with the COVID crisis of 2020. The National Professional Council of Allergology wanted to survey its members in this regard. 82.1% did not use this tool before the crisis but during it 86.4% of the doctors did it and 66.8% still do it in 2021. The teleconsultation is used mainly for the renewal of an allergen immunotherapy, symptomatic treatments and to announce a biological assessment. One in two allergists find it “interesting” to be able to receive new patients in this way, especially for patients in a medical desert, with a history of drug allergy or chronic urticaria. 57.3% think they save time thanks to teleconsultation. We note that this tool has become a habit of allergists who have known how to appropriate and adapt it to their practice.

Mesenchymal stem/stromal cell therapy in atopic dermatitis and chronic urticaria: immunological and clinical viewpoints.

Allergic diseases are immune-mediated diseases. Allergies share a common immunopathogenesis, with specific differences according to the specific disease. Mesenchymal stem/stromal cells (MSCs) have been applied to people suffering from allergic and many other diseases. In this review, the immunologic roles of MSCs are systemically reviewed according to disease immunopathogenesis from a clinical viewpoint. MSCs seem to be a promising therapeutic modality not only as symptomatic treatments but also as causative and even preventive treatments for allergic diseases, including atopic dermatitis and chronic urticaria.

Anxiety disorder in allergic patients during COVID-19 pandemic

Background: Since the beginning of the spread of COVID-19, a lot of studies have been published describing the disease, its impact on other medical conditions, and the psychological consequences derived from the state of alarm and the confinement. However, no literature has been published regarding the impact of the pandemic situation on allergic patients. Objective: Assess and describe the appearance and development of an anxiety disorder in allergic patients during COVID-19 confinement measures due to the pandemic situation. Method: A descriptive observational study of patients aged 18-65 years attended by phone appointment at the Allergy department of Hospital Quironsalud Barcelona between March and May 2020. Those who had been diagnosed with any mental illness or psychological disorder, were excluded. All individuals gave their consent. The Goldberg scale was used for the diagnose of anxiety disorder. All analysis were performed using the Statistical software package SPSS version 20. A p value <0.05 was considered significant. Results: A total of 104 allergic patients were included (51.9% males, 50% females). Mean age was 39.1 years (20-66). The allergic history included 81.7% rhinitis, 51% asthma, 9.6% food allergy and 8.7% chronic urticaria. The 81.7% were under allergen specific immunotherapy treatment. During the observation period, 72.1% of the patients presented new symptoms: 46.2% attributed them to their allergy condition, 10.6% to COVID-19 and 15.4% to anxiety. Only one patient was truly diagnosed with COVID-19. According to Goldberg Scale, 49% presented anxiety disorder. This group developed more symptoms during confinement (88%) than those who were not diagnosed with anxiety (56%) (p < 0.001). The perception of allergic symptoms was similar in both groups (47% and 45% respectively, p = 0.92), while the perception of anxiety symptoms was different between groups (25.5% vs. 5.6%, p = 0.028). The presence of asthma was not correlated with higher diagnosed anxiety (p = 0.11). Conclusion: It is well known that allergic and respiratory infectious symptoms have similar characteristics and, therefore, it could be difficult for allergic patients to make the difference between Covid-19 infection and allergic reaction. To our knowledge, this is the first study to document a clear diagnosis of anxiety among allergic patients during the COVID-19 state of alarm. It is extremely important to take this condition into account to achieve a global good control of our patients.

How to study inducible urticaria? Development of diagnostic circuits for more than one stimulus

Background: Inducible Urticaria (IU) is a type of Chronic Urticaria (CU) that occurs after exposure to physical and non-physical stimuli The diagnosis is based on patient history and provocation tests, which reproduce the symptoms after exposure to an appropriate triggering stimulus. IU may be present in patients with history of Chronic Spontaneous Urticaria (CSU) Our objective was to establish standardized protocols through diagnostic circuits that included tests for different stimuli in the same visit, reduce consultation time and evaluate their effectiveness and safety. Method: We designed 4 circuits where different test instruments for IU were included: Temptest, Fric-Test, Calibrated Dermographometer, Standard laboratory vortex and suspension of weights (7 kg.) over the shoulder. The circuits were: • Basic Circuit (BC): Dermographism, Temperature (cold and heat), Pressure (delayed an acute) and Vibratory Urticaria (Diagram 1) • Cold Urticaria Circuit (CUC): CB plus Ice Cube Test • Aquagenic Urticaria Circuit (AqUC): CB plus Aquagenic test • Autoimmune Urticaria Circuit (AuUC): CB plus Autologous Serum Skin Test (ASST) Cholinergic Urticaria tests were not included due to COVID pandemic restrictions, nor tests for Solar Urticaria as the necessary technical means were not available. For 6 months, we selected 51 patients with urticaria history lasting for more than 6 weeks. The circuit chosen for the study depended on the initial clinical suspicion. If there was no clear triggering stimulus, the BC was performed which includes the most frequent causes of IU. Results: Of the total number of patients studied, BC was applied to 82.4%, CUC to 7.8%, AqUC to 7.8% and AuUC to 2%. The most frequent diagnosis was Dermographism in 47.05% of the patients. This diagnosis was also present in some patients with CSU. The maximum time to perform these circuits was 30 minutes. None of the patients studied presented systemic reactions, anaphylaxis or other unexpected reactions. Conclusion: We observed that the use of standardized circuits in patients with suspected UI makes it possible to study more than one stimulus and to give the appropriate recommendations in each case. These tests are easy to apply and help to optimize study time. Besides, they allow the detection of physical or non-physical stimuli associated with SCU. Given that no patient presented adverse reactions, it appears to be a safe test. (Figure Presented).