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.

Impact of COVID-19 pandemic on the course of refractory chronic spontaneous urticaria under omalizumab treatment.

BACKGROUND: The course of chronic spontaneous urticaria (CSU) can be influenced by infections, depression, and stress. OBJECTIVE: Our aim was to investigate the impact of the COVID-19 pandemic on the course of refractory CSU together with patient adherence to omalizumab and treatment adjustments. METHODS: Urticaria Activity Score (UAS7) was used to assess disease activity. Fear of COVID-19 Scale (FC-19s), and Depression Anxiety Stress Scale (DASS-21s) were performed to assess mental health status. All scales were performed during the Quarantine Period (QP) and Return to the Normal Period (RTNP). UAS7 Before Pandemic (BP) was recorded from the patients medical records. RESULTS: The authors evaluated 104 omalizumab-receiving CSU patients. UAS7 scores during QP were significantly higher than those in RTNP and BP (p < 0.01). DASS-21 and FC-19 scores were significantly higher during QP compared to RTNP (p < 0.01). Nineteen (18.2%) patients ceased omalizumab, 9 patients prolonged the intervals between subsequent doses during the pandemic. UAS7 scores in QP were significantly higher in patients who ceased omalizumab than in those who continued (p < 0.001). Among patients who continued omalizumab, 22.4% had an increase in urticaria activity and higher FC-19 scores in comparison with those with stable disease activity (p = 0.008). STUDY LIMITATIONS: The small sample size of patients with prolonged intervals of omalizumab and the lack of mental health evaluation with the same tools prior to the study. CONCLUSION: Fear induced by COVID-19 can determine an increase in disease activity. Therefore, patients on omalizumab should continue their treatment and prolonged interval without omalizumab can be considered in patients with good urticaria control.

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.

Urticaria and angioedema in children and adolescents: diagnostic challenge.

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.

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.

Pediatric chronic spontaneous urticaria: a brief clinician's guide.

INTRODUCTION: 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. AREAS COVERED: 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. EXPERT OPINION: 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.

The Role of Cetirizine in the Changing Landscape of IV Antihistamines: A Narrative Review.

Since 1955, the only available H1 antihistamines for intravenous administration have been first-generation formulations and, of those, only intravenously administered (IV) diphenhydramine is still approved in the USA. Orally administered cetirizine hydrochloride, a second-generation H1 antihistamine, has been safely used over-the-counter for many years. In 2019, IV cetirizine was approved for the treatment of acute urticaria. In light of this approval, this narrative review discusses the changing landscape of IV antihistamines for the treatment of histamine-mediated conditions. Specifically, IV antihistamines will be discussed as a treatment option for acute urticaria and angioedema, as premedication to prevent infusion reactions related to anticancer agents and other biologics, and as an adjunct treatment for anaphylaxis and other allergic reactions. Before the development of IV cetirizine, randomized controlled trials of IV antihistamines for these indications were lacking. Three randomized controlled trials have been conducted with IV cetirizine versus IV diphenhydramine in the ambulatory care setting. A phase 3 trial of IV cetirizine 10 mg versus IV diphenhydramine 50 mg was conducted in 262 adults who presented to the urgent care/emergency department with acute urticaria requiring antihistamines. For the primary efficacy endpoint, defined as change from baseline in a 2-h patient-rated pruritus score, non-inferiority of IV cetirizine to IV diphenhydramine was demonstrated (score - 1.6 vs - 1.5, respectively; 95% CI - 0.1, 0.3). Compared with IV diphenhydramine, IV cetirizine demonstrated fewer adverse effects including less sedation, a significantly shorter length of stay in the treatment center, and fewer returns to the treatment center at 24 and 48 h. Similar findings were demonstrated in another phase 2 acute urticaria trial and in a phase 2 trial assessing IV cetirizine for pretreatment for infusion reactions in the oncology/immunology setting. IV cetirizine is associated with similar patient outcomes, fewer adverse effects, and increased treatment center efficiency than IV diphenhydramine.

[Urticaria associated with COVID-19 in allergic patients. A case series]. / Urticaria asociada a COVID-19 en pacientes alérgicos. Serie de casos.

INTRODUCTION: In December 2019, a new coronavirus was identified as the causal agent of the 2019 coronavirus disease (COVID-19) with a wide clinical spectrum that goes from asymptomatic cases to critical and fatal cases. Its usual manifestations are fever, cough, and fatigue; although some cases present skin lesions. CASES REPORT: The first case was a 30-year-old woman with a history of controlled solar urticaria who presented erythematous and pruritic wheals in malar and cervical regions and extremities; associated with general malaise, headaches, and nausea, in whom the presence of COVID-19 was confirmed; her condition improved with a quadruple dose of antihistamines. The second case was a 47-year-old woman with a history of wasp sting anaphylaxis, without mastocytosis, who presented nasal congestion, headaches, and hypogeusia associated with generalized, erythematous, and pruritic wheals, with confirmation of COVID-19; her condition improved with quadruple doses of antihistamines. CONCLUSIONS: Cutaneous manifestations associated with COVID-19 are frequent and can be classified as inflammatory and vascular. Among them, urticarial lesions occupy the fourth place, and although there could be some predominance of these in patients with a history of allergies, more studies are required to define an association.

Introducción: En diciembre de 2019 fue identificado un nuevo coronavirus como agente causal de la enfermedad por coronavirus del 2019 con un amplio espectro clínico, desde casos asintomáticos hasta críticos y fatales. Generalmente se manifiesta con fiebre, tos y fatiga, aunque algunos casos se presentan con lesiones cutáneas. Reporte de casos: El primer caso es una mujer de 30 años con antecedente de urticaria solar controlada quien presentó habones eritematosos y pruriginosos en región malar, cervical y extremidades, asociado a malestar general, cefalea y náuseas, en quien se confirmó la presencia de COVID-19, y mejoró con antihistamínicos a dosis cuádruple. El segundo caso es una mujer de 47 años con antecedente de anafilaxia por picadura de avispa, sin mastocitosis, quien presentó congestión nasal, cefalea e hipogeusia asociado a habones generalizados, eritematosos y pruriginosos, con confirmación de COVID-19, y mejoría con dosis cuadruple de antihistamínicos. Conclusiones: Las manifestaciones cutáneas asociadas a COVID-19 son frecuentes y se pueden clasificar en inflamatorias y vasculares. Dentro de ellas, las lesiones urticariales ocupan el cuarto lugar, y aunque podría existir algún predominio de estas en pacientes con antecedentes de alergias, se necesitan más estudios para definir una asociación.

[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.

What the physicians should know about mast cells, dendritic cells, urticaria, and omalizumab during COVID-19 or asymptomatic infections due to SARS-CoV-2?

Coronavirus disease (COVID-19) pandemic presents several dermatological manifestations described in the present indexed literature, with around 700 cases reported until May 2020, some described as urticaria or urticarial rashes. Urticaria is constituted by evanescent erythematous-edematous lesions (wheals and flare), which does not persist in the same site for more than 24 to 48 hours and appears in other topographic localization, resolving without residual hyper pigmentation. During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, some cytokines are synthesized, including Interferon (IFN) type I, TNF-α, and chemokines which may induce mast cells (MCs) and basophils degranulation by mechanisms similar to the autoinflammatory monogenic or polygenic diseases. In this article, we discuss the spectrum of the urticaria and urticarial-like lesions in the COVID-19's era, besides other aspects related to innate and adaptative immune response to viral infections, interactions between dermal dendritic cells and MCs, and degranulation of MCs by different stimuli. Plasmacytoid dendritic cells share, in allergic patients, expression of the high-affinity IgE receptors on cell membranes and demonstrated a low pattern of type I IFN secretion in viral infections. We discuss the previous descriptions of the effects of omalizumab, a monoclonal antibody directed to IgE and high-affinity IgE receptors, to improve the IFN responses and enhance their antiviral effects.

A case for palliative dermatology: COVID-19-related dermatoses.

The unprecedented coronavirus disease 2019 (COVID-19) pandemic has challenged health care systems in different ways. In the United Kingdom, various subspecialties are deployed to the wards to help medical workforce in the frontlines, with dermatologists helping with general medical wards and on-calls. We present a case of COVID-19-related urticaria manifesting in a palliative setting and responding well to systemic antihistamine. This pandemic has highlighted a new subspecialty that should be explored and researched-palliative dermatology-bridging elements of dermatology with the concepts of palliative medicine. As dermatologists, we should be in the position to help with the last stages of a patient's journey.

The impact of COVID-19 pandemic on the management of patients with chronic urticaria: An observational two-center study from Turkey.

The Coronavirus Disease 2019 (COVID-19) outbreak significantly affected the clinical practice in hospitals and the management of many diseases. The aim of this study was to evaluate the effect of pandemic-related factors on the severity and course of chronic urticaria (CU). A total of 194 CU patients who were on regular follow-up, were enrolled in the study. The disease activity was assessed by means of the weekly urticaria activity score (UAS7) and urticaria control test (UCT). Patients were divided into two subgroups according to their disease aggravation as "aggravated" and "non-aggravated". Two groups were compared in terms of demographic, clinical, COVID-19-associated parameters, and parameters related with the effect of COVID-19 pandemic on CU management. The omalizumab use was statistically higher (P = .017), and the systemic corticosteroid use was statistically lower (P = .025) in the "aggravated" group. Adherence to quarantine was significantly lower in the "aggravated" group (P = .027). 173 patients (89.2%) were unable to contact a dermatologist during the pandemic. Among 186 patients who received treatment for CU before the pandemic, 48 (25.8%) did not continue the existing treatment during the pandemic. CU aggravated in one patient with COVID-19 and remained stable in the other. This study showed that CU patients, especially those on omalizumab therapy, had difficulties in attending medical care and even in the maintenance of their existing therapies during the pandemic. Creating novel follow-up and treatment models as well as the increased use of teledermatology might be beneficial in the management of this life-disturbing condition.