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.

Hypocomplementemic urticarial vasculitis case with hemophagocytic lymphohistiocytosis following SARS-CoV-2 mRNA vaccination.

A 61-year-old man with no previous record of autoimmune disease developed fever, polyarthralgia, purpura, and urticaria-like rash 2 weeks after the first dose of the Moderna mRNA-1273 vaccine, and symptoms deteriorated following the second dose. He presented reduced erythrocyte and platelet counts, hyperferritinemia, high sIL-2R levels, and severe hypocomplementemia. We diagnosed hypocomplementemic urticarial vasculitis (HUVS), and his symptoms as well as laboratory findings improved following treatment with mPSL 1000 mg/day for 3 days and PSL 40 mg/day. Twelve weeks following treatment initiation, the patient relapsed with fever, sore throat, pancytopenia, and hyperferritinemia when the PSL dose was reduced to 12.5 mg/day. Bone marrow biopsy and MRI presented fatty marrow and hemophagocytosis. The patient's blood cells started recovering using ATG + CsA + EPAG therapy for hemophagocytic lymphohistiocytosis (HLH). This is the first case report of HUVS and HLH following SARS-CoV-2 mRNA vaccination. It is presumed that SARS-CoV-2 mRNA vaccine can induce the excessive production of certain types of cytokines, such as TNF-α, IL-1, IL-4, IL-5, IL-6, and IL-17 as a consequence of IL-6 Amplification (IL-6 Amp). SARS-CoV-2 mRNA-vaccines can cause disruption of immune homeostasis in healthy individuals. An extremely rare disease of HUVS complicated by HLH can be developed as a consequence.

A favipiravir-induced angioedema and urticaria in a COVID-19 patient.

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.

In Urticarial Vasculitis, Long Disease Duration, High Symptom Burden, and High Need for Therapy Are Linked to Low Patient-Reported Quality of Life.

BACKGROUND: Urticarial vasculitis (UV) is a rare and difficult-to-treat chronic skin disease defined by long-lasting urticarial lesions and the histopathologic finding of leukocytoclastic vasculitis. As of yet, little is known about UV patients' perspective on the disease. OBJECTIVE: To assess UV patients' perspective on the clinical course, treatment response, greatest challenges, and quality-of-life (QOL) impairment. METHODS: A web-based questionnaire was disseminated in a Facebook group of patients with UV. Patients with UV confirmed by skin biopsy were included. RESULTS: Patients with UV had a mean age of 47.3 ± 12.3 years and were mostly female (94.3%; n = 82 of 87). The median delay in diagnosis was 8.1 months (interquartile range, 2.0-46.3). Normocomplementemia and hypocomplementemia were present in 54.0% (n = 27) and 46.0% (n = 23) of 50 patients, respectively. Most patients with UV (51.8%; n = 43 of 83) reported severely decreased QOL due to their disease. Low QOL was also the most frequently reported greatest challenge for patients with UV (40.7%), followed by the long-standing course of UV with frequent relapses (14.8%). Low QOL correlated with long disease duration (r = 0.298; P = .02) and high numbers of clinical symptoms (r = 0.294; P = .007). Patients with UV with allergies, lung diseases, and chronic infections reported lower QOL. Patients with UV with low QOL were treated with analgesics, dapsone, montelukast, omalizumab, and colchicine more often than patients with UV with higher QOL (P < .05 for all). CONCLUSIONS: Our results show a considerable impairment in QOL in patients with UV associated with long disease duration, high symptom burden, and a high need for therapy. Improvement of the management of UV by further research is necessary.

Delayed systemic urticarial reactions following mRNA COVID-19 vaccination.

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.

BASCULE syndrome in a child with prior asymptomatic COVID-19 infection.

BASCULE syndrome, characterized by Bier anemic spots, cyanosis, and an urticaria-like eruption, has been described as a benign vasomotor dermatosis that occurs in the setting of transient tissue hypoxia. It has been postulated that dermal ischemia triggers an exaggerated vasoconstrictive arteriolar reaction, which then causes a paradoxical urticarial rash by an unknown mechanism. In patients with COVID-19, there is evidence of angiocentric inflammation leading to vasoconstriction, endothelial damage, and thrombosis. We present a case of acute-onset BASCULE syndrome appearing after asymptomatic infection with COVID-19. BASCULE syndrome should be considered in the expanding spectrum of dermatologic manifestations associated with COVID-19.

[Cutaneous manifestations in patients with COVID-19 with significant attention to urticaria]. / Manifestaciones cutáneas en los pacientes con COVID-19 con especial atención en la urticaria.

OBJECTIVES: To describe the most frequent dermatological conditions observed in COVID-19 patients and to determine whether their presence could be used to establish an early diagnosis or to predict the progression of the infection. METHODS: There was a review in PubMed/MEDLINE and EMBASE of all the articles that had been published between January 1st and November 1st, 2020, with the search terms focused on "SARS-CoV-2", "COVID-19" and "Skin diseases". RESULTS: Eighty three studies met the inclusion criteria. Skin lesions have been reported in 0.2 % of the patients. The most frequently reported dermatoses were: maculopapular/ morbilliform rashes, urticaria and angioedema, chilblain-like acral pattern, and vesicular lesions. Among researchers, there are differences of opinion about a possible diagnostic or prognostic value of the skin diseases that are associated to the infection. CONCLUSIONS: It is advisable to consider the diagnosis of SARS-CoV-2 infection in patients who call the doctor for skin lesions, urticaria, or angioedema, with or without other symptoms of the infection, especially if there is a previous history of recent exposure to other infected subjects.

Objetivos: Describir las afecciones dermatológicas más frecuentes en los pacientes con la COVID-19 y precisar si su presencia puede ser utilizada para establecer un diagnóstico temprano o para predecir la evolución de la infección. Métodos: Se realizó una revisión en PubMed/MEDLINE y EMBASE de todos los artículos publicados entre enero 1 y noviembre 1 de 2020, con los términos de la búsqueda centrados en "SARS-CoV-2", "COVID-19" y "Enfermedades cutáneas". Resultados: Cumplieron los criterios de inclusión 83 estudios. Lesiones de la piel han sido reportadas en 0.2 % de los pacientes. Las erupciones maculopapulares/morbiliformes, la urticaria y el angioedema, el patrón acral parecido a sabañones y las lesiones vesiculares fueron las dermatosis más frecuentemente informadas. Existen diferencias de opinión entre los investigadores, acerca de un posible valor diagnóstico o pronóstico de las afecciones cutáneas asociadas con la infección. Conclusiones: Es recomendable considerar el diagnóstico de la infección por SARS-CoV-2 en pacientes que consultan por presentar lesiones cutáneas, urticaria o angioedema con o sin otros síntomas de la infección y en especial si existe algún antecedente de exposición reciente a otros sujetos infectados.

Cutaneous Manifestations of COVID-19 in the Inpatient Setting.

Cutaneous findings have increasingly been reported in patients with coronavirus disease 2019 (COVID-19). This review discusses associated skin findings in patients with COVID-19 in the inpatient setting, ranging from vasculopathy-related lesions associated with high hospitalization rate and poor prognosis to inflammatory vesicular and urticarial eruptions that are rarely associated with prolonged hospitalization. We also discuss other reported COVID-19 cutaneous manifestations such as Sweet's syndrome, purpuric eruptions, and Multisystem Inflammatory Syndrome in Children. Although the relationship between dermatologic changes and COVID-19 disease progression is not fully elucidated, familiarity with cutaneous manifestations is valuable for physicians caring for patients hospitalized with COVID-19 and may help improve disease recognition and care.

Cutaneous Manifestations of COVID-19: Characteristics, Pathogenesis, and the Role of Dermatology in the Pandemic.

Cutaneous manifestations of COVID-19-SARS-CoV-2-are common and varied. Morbilliform, vesicular, and urticarial eruptions may be nonspecific initial features of the disease. Chilblainlike lesions on the fingers or toes typically occur as part of a resolution phase, signifying a milder course, whereas livedoid lesions and retiform purpura are associated with coaguloapthy and more severe disease. Additionally, a severe Kawasaki-like multisystem inflammatory syndrome rarely is seen in children. This diverse range of cutaneous manifestations in COVID-19 reflects a spectrum of host immunologic responses to SARS-CoV-2 and may inform disease pathophysiology.

Case report: SARS-CoV-2-induced urticaria or just a concomitance?

The association between urticaria and different virus infections has been reported in many studies. Different virus infections have been reported to be comorbidities of spontaneous urticaria. In this paper, we report the case of a male patient with acute urticaria 7 days after he left the hospital where he was treated for coronavirus disease 2019 (COVID-19). This infection may act as a causative or a facilitating factor for the initiation of acute urticaria and additional cofactors such as stress may contribute for the urticaria phenotype to be expressed. Additional facts for severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) virus in future will clarify if urticarial rash is one of the COVID's multiple faces.

Etiological and predictive factors of pediatric urticaria in an emergency context.

BACKGROUND: Urticaria is common in pediatric population and is caused by various etiologies which usually differ among different age groups. The different etiologies require different management strategies. Thus, understanding detailed of the etiologies of urticaria in children would help pediatricians to perform appropriate initial treatment. METHODS: A cross-sectional epidemiological study of all patients aged under 18-year-old with the diagnosis of urticaria from any causes entered in the emergency department during January 1st, 2016 to December 31st, 2019 by collecting the data from the Health Object Program®, an authorized electronic medical records program, at the Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Thailand. RESULTS: There were total of 515 urticaria patients aged under 18 years old at the emergency department. The ages of patients ranged from 8 months to 18 years with a median age of 7 years (IQR 3.17-12.08). The majority of the patients were in the preschool-aged group (40.97%), followed by the school-aged (28.16%), adolescent (22.14%), and infant (8.74%). Six major etiologic categories were identified in the present study. The most common cause of urticaria was infection (51.26%), followed by idiopathic urticaria (34.37%), inhalants (6.99%), drugs (4.08%), foods (2.52%), and insect stings (0.78%). CONCLUSIONS: Having underlying allergic diseases had a strong association with all identified causes of urticaria in the study population, of which, food and inhalation etiologies had a significant difference when compared to the other identified causes. The present study has found that infection was the most common cause of acute urticaria in children. This etiology (infection-induced urticaria) usually presents concurrent with fever, however, non-febrile symptoms were also presented. Therefore, in the pediatric population, pediatricians should always look for infection as the cause of urticaria even in patients without pyrexia.