Urticaria exacerbations and adverse reactions in patients with chronic urticaria receiving COVID-19 vaccination: Results of the UCARE COVAC-CU study.

BACKGROUND: Concern about disease exacerbations and fear of reactions after coronavirus disease 2019 (COVID-19) vaccinations are common in chronic urticaria (CU) patients and may lead to vaccine hesitancy. OBJECTIVE: We assessed the frequency and risk factors of CU exacerbation and adverse reactions in CU patients after COVID-19 vaccination. METHODS: COVAC-CU is an international multicenter study of Urticaria Centers of Reference and Excellence (UCAREs) that retrospectively evaluated the effects of COVID-19 vaccination in CU patients aged ≥18 years and vaccinated with ≥1 dose of any COVID-19 vaccine. We evaluated CU exacerbations and severe allergic reactions as well as other adverse events associated with COVID-19 vaccinations and their association with various CU parameters. RESULTS: Across 2769 COVID-19-vaccinated CU patients, most (90%) received at least 2 COVID-19 vaccine doses, and most patients received CU treatment and had well-controlled disease. The rate of COVID-19 vaccination-induced CU exacerbation was 9%. Of 223 patients with CU exacerbation after the first dose, 53.4% experienced recurrence of CU exacerbation after the second dose. CU exacerbation most often started <48 hours after vaccination (59.2%), lasted for a few weeks or less (70%), and was treated mainly with antihistamines (70.3%). Factors that increased the risk for COVID-19 vaccination-induced CU exacerbation included female sex, disease duration shorter than 24 months, having chronic spontaneous versus inducible urticaria, receipt of adenovirus viral vector vaccine, having nonsteroidal anti-inflammatory drug/aspirin intolerance, and having concerns about getting vaccinated; receiving omalizumab treatment and Latino/Hispanic ethnicity lowered the risk. First-dose vaccine-related adverse effects, most commonly local reactions, fever, fatigue, and muscle pain, were reported by 43.5% of CU patients. Seven patients reported severe allergic reactions. CONCLUSIONS: COVID-19 vaccination leads to disease exacerbation in only a small number of CU patients and is generally well tolerated.

Prophylaxis of Upper Airway Infections in a Patient with Partial IgA Deficiency: Concurrent Use of Sublingual Immunotherapy with Inactivated Whole-Cell Bacterial Extract and Der p1.

Selective IgA deficiency is the most common type of primary immunodeficiency, but there is not yet a specific effective treatment. The most prevalent clinical manifestations are infectious diseases of the respiratory system. We report herein the case of an 11-year-old female with selective IgA deficiency and recurring episodes of respiratory infections associated with rhinitis and asthma. We evaluated the efficacy of sublingual immunotherapy combined with inactivated whole-cell bacterial extract and Der p1-specific immunotherapy. After 18 months of clinical follow-up, we observed a significant reduction in the number of episodes of respiratory infections associated with control of atopic diseases. We also observed a 3-fold increase in serum IgA levels compared to treatment initiation. This case demonstrates the potential utility of the concurrent use of sublingual immunotherapy with inactivated whole-cell bacterial extract and Der p1 for successful control of allergy and infection in partial selective IgA deficiency.

Imunopatologia da COVID-19 e suas implicações clínicas / COVID-19 immunopathology and its clinical implications

Compreender os mecanismos imunopatológicos envolvidos na evolução da COVID-19 é um desafio para a ciência mundial. A observação da existência de formas clínicas diferentes da doença, podendo ocorrer desde manifestações leves até formas graves, demonstra a complexidade da resposta imune desenvolvida frente à infecção pelo SARS-CoV-2. Nesta revisão da literatura, utilizamos as bases de dados PubMed, MEDLINE, LILACS, SciELO a partir de dezembro de 2019, quando surgiram os primeiros casos da doença. A relação entre as diferentes formas clínicas da COVID-19 com o desenvolvimento da resposta imune foi amplamente discutida. As diferenças da evolução da COVID-19 em crianças e idosos foram avaliadas focalizando aspectos da resposta imune que podem conferir prognóstico favorável ou risco de desenvolvimento de formas clínicas graves. Particularidades da infecção pelo SARS-CoV-2 em pacientes com imunossupressão e em portadores de asma foram analisadas. Os mecanismos imunopatológicos envolvidos no desenvolvimento das formas graves da COVID-19 foram abordados com ênfase no fenômeno "tempestade de citocinas".

Understanding the immunopathological mechanisms involved in the evolution of COVID-19 is a challenge for science worldwide. The observed existence of several clinical forms of the disease with mild to severe manifestations demonstrates the complexity of the immune response to SARS-CoV-2 infection. In this literature review, we searched the PubMed, MEDLINE, LILACS, SciELO databases for studies published after December 2019, when the first cases of the disease were described. The relationship between the different clinical forms of COVID-19 and the development of immune response was widely discussed. The differences in the evolution of COVID-19 in children and elderly were evaluated focusing aspects of the immune response that may confer favorable prognosis or risk of developing severe clinical forms. Particularities of SARS-CoV-2 infection in patients with immunosuppression and in asthma patients were analyzed. The immunopathological mechanisms involved in the development of severe forms of COVID-19 were addressed, with emphasis on the cytokine storm phenomenon.

Copaiba oil suppresses inflammation in asthmatic lungs of BALB/c mice induced with ovalbumin.

Asthma is a chronic inflammatory disease that represents high hospitalizations and deaths in world. Copaiba oil (CO) is popularly used for relieving asthma symptoms and has already been shown to be effective in many inflammation models. This study aimed to investigate the immunomodulatory relationship of CO in ovalbumin (OVA)-induced allergic asthma. The composition of CO sample analyzed by GC and GC-MS and the toxicity test was performed in mice at doses of 50 or 100 mg/kg (by gavage). After, the experimental model of allergic asthma was induced with OVA and mice were orally treated with CO in two pre-established doses. The inflammatory infiltrate was evaluated in bronchoalveolar lavage fluid (BALF), while cytokines (IL-4, IL-5, IL-17, IFN-γ, TNF-α), IgE antibody and nitric oxide (NO) production was evaluated in BALF and lung homogenate (LH) of mice, together with the histology and histomorphometry of the lung tissue. CO significantly attenuated the number of inflammatory cells in BALF, suppressing NO production and reducing the response mediated by TH2 and TH17 (T helper) cells in both BALF and LH. Histopathological and histomorphometric analysis confirmed that CO significantly reduced the numbers of inflammatory infiltrate in the lung tissue, including in the parenchyma area. Our results indicate that CO has an effective in vivo antiasthmatic effect.

Punctuated 88% Phenol Peeling for the Treatment of Facial Photoaging: A Clinical and Histopathological Study.

BACKGROUND: Phenol peeling is considered an important agent in the treatment of facial rejuvenation; however, its use has limitations due to its high potential for side effects. OBJECTIVE: This article proposes a new peeling application technique for the treatment of photoaging, aiming to evaluate, clinically and histopathologically, the efficacy of a new way of applying 88% phenol, using a punctuated pattern. METHODS: The procedure was performed in an outpatient setting, with female patients, on static wrinkles and high flaccidity areas of the face. Accompanying photographs and skin samples were taken for histopathological analysis before and after treatment. RESULTS: It was shown that 88% phenol applied topically using a punctuated technique is effective in skin rejuvenation. CONCLUSION: The authors thus suggest, based on this new proposal, that further studies be conducted with a larger group of patients to better elucidate the action mechanisms of 88% phenol. This new form of application considerably reduced patients' withdrawal from their regular activities, besides reducing the cost, compared with the conventional procedure.

ß-Caryophyllene ameliorates the development of experimental autoimmune encephalomyelitis in C57BL/6 mice.

Multiple sclerosis is the most common autoimmune inflammatory and demyelinating disease of the central nervous system. The experimental autoimmune encephalomyelitis (EAE) is an appropriate and a well-establish model for studying the pathogenesis of MS. ß-caryophyllene (BCP), a natural sesquiterpene found in many plant species, is a potent anti-inflammatory compound. Herein we investigated the in vitro and in vivo immunomodulatory effects of BCP on C57BL/6 mice induced with EAE. BCP was in vitro evaluated (4, 20, and 40µM) on splenocytes obtained from EAE-induced C57BL/6 mice, and in vivo (25 or 50mg/kg/day) orally administered on EAE-mice. The clinical course, body weight, cytokines and oxygen radicals production were investigated in C57BL/6 EAE-mice. In vitro and in vivo immunological responses were evaluated by ELISA, and CNS sections were stained by hematoxylin and eosin methods The in vitro production of H2O2, NO, IFN-γ, and TNF- α was inhibited by BCP (20 and 40µM) in cultured cells from EAE-mice. BCP (25 and 50mg/kg/day) reduced clinical score and severity of EAE and inhibited H2O2, NO, TNF-α, IFN-γ and, IL-17 production. EAE-mice, orally treated with BCP (mainly at 50mg/kg/day), displayed levels of cytokines and clinical signs similar to animals with no EAE disease, demonstrating the therapeutic action of BCP on EAE animals. Histopathological and histomorphometric analysis confirmed that BCP treatment significantly reduced the numbers of inflammatory infiltrates and attenuated neurological damages in the CNS of EAE-mice.

Hyperoxia promotes polarization of the immune response in ovalbumin-induced airway inflammation, leading to a TH17 cell phenotype.

Previous studies have demonstrated that hyperoxia-induced stress and oxidative damage to the lungs of mice lead to an increase in IL-6, TNF-α, and TGF-ß expression. Together, IL-6 and TGF-ß have been known to direct T cell differentiation toward the TH17 phenotype. In the current study, we tested the hypothesis that hyperoxia promotes the polarization of T cells to the TH17 cell phenotype in response to ovalbumin-induced acute airway inflammation. Airway inflammation was induced in female BALB/c mice by intraperitoneal sensitization and intranasal introduction of ovalbumin, followed by challenge methacholine. After the methacholine challenge, animals were exposed to hyperoxic conditions in an inhalation chamber for 24 h. The controls were subjected to normoxia or aluminum hydroxide dissolved in phosphate buffered saline. After 24 h of hyperoxia, the number of macrophages and lymphocytes decreased in animals with ovalbumin-induced airway inflammation, whereas the number of neutrophils increased after ovalbumin-induced airway inflammation. The results showed that expression of Nrf2, iNOS, T-bet and IL-17 increased after 24 of hyperoxia in both alveolar macrophages and in lung epithelial cells, compared with both animals that remained in room air, and animals with ovalbumin-induced airway inflammation. Hyperoxia alone without the induction of airway inflammation lead to increased levels of TNF-α and CCL5, whereas hyperoxia after inflammation lead to decreased CCL2 levels. Histological evidence of extravasation of inflammatory cells into the perivascular and peribronchial regions of the lungs was observed after pulmonary inflammation and hyperoxia. Hyperoxia promotes polarization of the immune response toward the TH17 phenotype, resulting in tissue damage associated with oxidative stress, and the migration of neutrophils to the lung and airways. Elucidating the effect of hyperoxia on ovalbumin-induced acute airway inflammation is relevant to preventing or treating asthmatic patients that require oxygen supplementation to reverse the hypoxemia.

Copaiba oil suppresses inflammatory cytokines in splenocytes of C57Bl/6 mice induced with experimental autoimmune encephalomyelitis (EAE).

Experimental autoimmune encephalomyelitis (EAE) is a murine autoimmune disease used to study multiple sclerosis. We have investigated the immunomodulatory effects of copaiba oil (100, 50 and 25 µg/mL) on NO, H2O2, TNF-α, IFN-γ and IL-17 production in cultured cells from EAE-mice. Copaiba oil (100 µg/mL) inhibited H2O2, NO, IFN-γ TNF-α and IL-17 production spontaneously or after ConA and MOG35-55 stimulation. It is suggested that copaiba oil acts on the mechanism of development of EAE by IFN-γ, IL-17 and TNF-α inhibition, modulating the immune response on both Th1 and Th17 cells.

Protective effects of Baccharis dracunculifolia leaves extract against carbon tetrachloride- and acetaminophen-induced hepatotoxicity in experimental animals.

In this work we investigated the in vivo protective effects of Baccharis dracunculifolia leaves extract (BdE) against carbon tetrachloride (CCl4)- and acetaminophen (APAP)-induced hepatotoxicity. Total phenolic content, total flavonoid content, antioxidant DPPH radical scavenging activity, and HPLC analysis were performed. Our results showed that pretreatment with BdE significantly reduced the damage caused by CCl4 and APAP on the serum markers of hepatic injury, AST, ALT, and ALP. Results were confirmed by histopathological analysis. Phytochemical analysis, performed by HPLC, showed that BdE was rich in p-coumaric acid derivatives, caffeoylquinic acids and flavonoids. BdE also showed DPPH antioxidant activity (EC50 of 15.75±0.43 µg/mL), and high total phenolic (142.90±0.77 mg GAE/g) and flavonoid (51.47±0.60 mg RE/g) contents. This study indicated that B. dracunculifolia leaves extract has relevant in vivo hepatoprotective properties.

The effect of essential oil of Syzygium cumini on the development of granulomatous inflammation in mice

The anti-inflammatory and apoptotic activity of the essential oil of Syzygium cumini (L.) Skeels, Myrtaceae, leaves was investigated in vivo. The anti-inflammatory action and chronic granulomatous inflammation in BALB/c mice, intravenously infected with Mycobacterium bovis, BCG, (Bacillo Calmet Guerim), was judged by measuring and classifying the granulomas formed in the hepatic parenchyma. The degree of apoptosis in the inflammatory cells was also measured. A reduction in the granulomatous area and a change in the pattern of the granulomas were found. Anti-mycobacterial activity of the essential oil against M. bovis was detected in vitro by an interferometric method in liquid culture medium. The chemical constituents of the essential oil were determined by GC/MS. Higher yields of the essential oil of S. cumini leaves were obtained by extraction in a Clevenger apparatus when the fresh leaves were previously frozen as a pre-processing step. The essential oil obtained from this plant demonstrated a statistically significant and dramatic effect in the chosen model system.

Low-level laser reduces the production of TNF-α, IFN-γ, and IL-10 induced by OVA.

Delayed, or type IV, hypersensitivity reactions are a useful model to study the effects of new substances on the immune system. In this study, the experimental model of the delayed type hypersensitivity (DTH) reaction to ovalbumin (OVA) was used to evaluate the immunomodulating effects of low-level laser therapy (LLLT), which is used as an adjuvant therapy in medicine, dentistry, and physical therapy because of its potential anti-inflammatory and analgesic effects observed in several studies. The effects of LLLT (λ 780 nm, 0.06 W/cm(2) of radiation, and fluency of 3.8 J/cm(2)) in reaction to ovalbumin in Balb/C mice were examined after the induction phase of the hypersensitivity reaction. The animals treated with azathioprine (AZA), the animals that received a vehicle instead of ovalbumin, and those not immunized served as controls (n = 6 for each group). Footpad thickness measurements and hematoxylin-eosin histopathological exams were performed. Proliferation tests were also performed (spontaneous, in the presence of concanavalin A and ovalbumin) to determine the production in mononuclear cells cultures of tumor necrosis factor-alpha (TNF-α), INF-γ, and IL-10. In the group of animals irradiated with lasers and in the group treated with AZA, footpad thickness measurements were significantly reduced in comparison to the control group (p < 0.05). This reduction was accompanied by a very significant reduction in the density of the inflammatory infiltrate and by a significant reduction in the levels of TNF-α, INF-γ, and IL-10. LLLT radiation was shown to have an immunomodulating effect on DTH to OVA in Balb/C mice.

Cellular profile of the peritumoral inflammatory infiltrate in squamous cells carcinoma of oral mucosa: Correlation with the expression of Ki67 and histologic grading.

BACKGROUND: Squamous cells carcinoma is the most important malignant tumor with primary site in the oral cavity and, given the great exposure of mucosa and lips to the etiologic factors of this neoplasm, its incidence is high. Investigation of the prognostic determinants is significant for the expectations of treatment proposal and cure of the patient. The local immune response represented by peritumoral inflammatory infiltrate is a possible prognostic factor. METHODS: In this study, oral mucosa samples of squamous cells carcinoma were analyzed, separated according to their histological classification as well as the phenotypical profile of the cells comprising the peritumoral inflammatory infiltrate was investigated by immunohistochemical method, in addiction, the cell proliferation index via protein Ki67 expression was determinated. RESULTS: The T lymphocytes made up most of this inflammatory infiltrate, and among these cells, there was a predominance of T CD8 lymphocytes relative to the T CD4 lymphocytes. The B lymhocytes were the second most visualized leucocyte cell type followed by macrophages and neutrophils. The immunohistochemical assessment of Ki-67 positive cells revealed a greater expression of this protein in samples of undifferentiated squamous cells carcinoma. CONCLUSION: The results suggest that the cellular immune response is the main defense mechanism in squamous cells carcinoma of oral mucosa, expressed by the large number of T lymphocytes and macrophages, and that the greatest intensity of local response may be associated with the best prognosis.