Introduction
The COVID‐19 pandemic dramatically disrupts health care around the globe. The impact of the pandemic on chronic urticaria (CU) and its management are largely unknown.
Aim
To understand ...how CU patients are affected by the COVID‐19 pandemic; how specialists alter CU patient management; and the course of CU in patients with COVID‐19.
Materials and Methods
Our cross‐sectional, international, questionnaire‐based, multicenter UCARE COVID‐CU study assessed the impact of the pandemic on patient consultations, remote treatment, changes in medications, and clinical consequences.
Results
The COVID‐19 pandemic severely impairs CU patient care, with less than 50% of the weekly numbers of patients treated as compared to before the pandemic. Reduced patient referrals and clinic hours were the major reasons. Almost half of responding UCARE physicians were involved in COVID‐19 patient care, which negatively impacted on the care of urticaria patients. The rate of face‐to‐face consultations decreased by 62%, from 90% to less than half, whereas the rate of remote consultations increased by more than 600%, from one in 10 to more than two thirds. Cyclosporine and systemic corticosteroids, but not antihistamines or omalizumab, are used less during the pandemic. CU does not affect the course of COVID‐19, but COVID‐19 results in CU exacerbation in one of three patients, with higher rates in patients with severe COVID‐19.
Conclusions
The COVID‐19 pandemic brings major changes and challenges for CU patients and their physicians. The long‐term consequences of these changes, especially the increased use of remote consultations, require careful evaluation.
The COVID‐19 pandemic severely impairs CU patient care, weekly number of patients decreased by more than 50%, and the rate of face‐to‐face consultations decreased by 62%. CU does not affect the course of COVID‐19 with only 4% of CU patients having a severe course of COVID‐19, but COVID‐19 results in CU exacerbation in one of three patients, with higher rates in patients with severe COVID‐19. Cyclosporine and systemic corticosteroids, but not antihistamines or omalizumab, are used less during the pandemic.
Abbreviations: CU, chronic urticarial; COVID‐19, coronavirus disease 2019; UCARE: urticaria centers of reference and excellence.
Human and animal fungal pathogens are a growing threat worldwide leading to emerging infections and creating new risks for established ones. There is a growing need for a rapid and accurate ...identification of pathogens to enable early diagnosis and targeted antifungal therapy. Morphological and biochemical identification methods are time-consuming and require trained experts. Alternatively, molecular methods, such as DNA barcoding, a powerful and easy tool for rapid monophasic identification, offer a practical approach for species identification and less demanding in terms of taxonomical expertise. However, its wide-spread use is still limited by a lack of quality-controlled reference databases and the evolving recognition and definition of new fungal species/complexes. An international consortium of medical mycology laboratories was formed aiming to establish a quality controlled ITS database under the umbrella of the ISHAM working group on “DNA barcoding of human and animal pathogenic fungi.” A new database, containing 2800 ITS sequences representing 421 fungal species, providing the medical community with a freely accessible tool at http://www.isham.org/ and http://its.mycologylab.org/ to rapidly and reliably identify most agents of mycoses, was established. The generated sequences included in the new database were used to evaluate the variation and overall utility of the ITS region for the identification of pathogenic fungi at intra-and interspecies level. The average intraspecies variation ranged from 0 to 2.25%. This highlighted selected pathogenic fungal species, such as the dermatophytes and emerging yeast, for which additional molecular methods/genetic markers are required for their reliable identification from clinical and veterinary specimens.
This systematic literature review (SLR) and meta-analysis assessed the efficacy and safety of pimecrolimus vs other topical treatments in patients with mild-to-moderate atopic dermatitis (AD), ...focusing on children and sensitive skin areas. An SLR was conducted in MEDLINE, Embase and Cochrane Library databases on January 15
th
, 2020, to identify randomized controlled trials (RCTs) with pimecrolimus as a study arm. Another SLR performed on October 5
th
, 2020 identified RCTs with a crisaborole study arm. Direct pair-wise meta-analysis was used to compare pimecrolimus with vehicle, tacrolimus or topical corticosteroids (TCS; n = 27 studies). Outcomes included Investigator’s Global Assessment (IGA) score 0/1 up to week 6 and adverse events. Pimecrolimus was more efficacious than vehicle in achieving IGA 0/1 up to week 6 in children, and similar safety profiles were observed with pimecrolimus and vehicle in children and the mixed population, including on sensitive skin. No significant differences in efficacy and safety were observed between pimecrolimus and tacrolimus 0.03%. Efficacy and safety were similar for pimecrolimus and mild medium potency TCS; mildly potent steroids caused transient epidermal thinning in sensitive skin areas (not seen with pimecrolimus). Pimecrolimus can be considered as a first-line option for mild-to-moderate AD, particularly in children and sensitive skin areas.
Systemic lupus erythematosus (SLE) is a prototypic systemic autoimmune disease. The T cell immunoglobulin and mucin domain (TIM) family is associated with autoimmune diseases, but its level of ...expression in the immune cells of patients with SLE is still uncertain. The aim of this study was to examine whether TIM-3 and Galectin-9 (Gal-9) contribute to the pathogenesis of SLE. In total, 30 patients with SLE and 30 healthy controls were recruited, and their levels of TIM-3 expression in peripheral blood mononuclear cells (PBMCs) were examined via flow cytometry. Meanwhile, the levels of Gal-9 expression in serum and in PBMCs were measured via an enzyme-linked immunosorbent assay (ELISA) kit and immunofluorescence staining, respectively. The relation between the level of TIM-3 or Gal-9 expression and the SLE disease activity index (SLEDAI) was also studied. Finally, the function of the TIM-3 and Gal-9 pathway in the pathogenesis of SLE was explored. Our results showed that the levels of expression of TIM-3 and Gal-9 on CD4
+
T cells, CD8
+
T cells, CD56
+
T cells and in serum in patients with SLE were significantly higher than those of healthy controls. We found that the level of Gal-9 expression was significantly higher in both serum and PMBCs of patients with SLE than in healthy controls. The up-regulation of TIM-3 and Gal-9 expression in patients with SLE was closely related to the SLEDAI scores. In addition, Gal-9 blocking antibody significantly inhibited CD3-stimulated PBMC proliferation and Th1-derived cytokines (IL-2, IFN-γ, and TNF-α), Th2-derived cytokines (IL-4, IL-10), a Th17-derived cytokine (IL-17A), and release of a pro-inflammatory factor (IL-6) in patients with SLE. The results suggest that increased expression of TIM-3 and Gal-9 may be a biomarker for SLE diagnosis and that the TIM-3 pathway may be a target for SLE treatment.
Background
Cold urticaria (ColdU), that is, the occurrence of wheals or angioedema in response to cold exposure, is classified into typical and atypical forms. The diagnosis of typical ColdU relies ...on whealing in response to local cold stimulation testing (CST). It can also manifest with cold‐induced anaphylaxis (ColdA). We aimed to determine risk factors for ColdA in typical ColdU.
Methods
An international, cross‐sectional study COLD‐CE was carried out at 32 urticaria centers of reference and excellence (UCAREs). Detailed history was taken and CST with an ice cube and/or TempTest® performed. ColdA was defined as an acute cold‐induced involvement of the skin and/or visible mucosal tissue and at least one of: cardiovascular manifestations, difficulty breathing, or gastrointestinal symptoms.
Results
Of 551 ColdU patients, 75% (n = 412) had a positive CST and ColdA occurred in 37% (n = 151) of the latter. Cold‐induced generalized wheals, angioedema, acral swelling, oropharyngeal/laryngeal symptoms, and itch of earlobes were identified as signs/symptoms of severe disease. ColdA was most commonly provoked by complete cold water immersion and ColdA caused by cold air was more common in countries with a warmer climate. Ten percent (n = 40) of typical ColdU patients had a concomitant chronic spontaneous urticaria (CSU). They had a lower frequency of ColdA than those without CSU (4% vs. 39%, p = .003). We identified the following risk factors for cardiovascular manifestations: previous systemic reaction to a Hymenoptera sting, angioedema, oropharyngeal/laryngeal symptoms, and itchy earlobes.
Conclusion
ColdA is common in typical ColdU. High‐risk patients require education about their condition and how to use an adrenaline autoinjector.
The COLD‐CE study was carried out at 32 UCAREs from 19 countries and four continents. Among 551 ColdU patients, 75% had positive local CST (i.e., typical ColdU) and ColdA occurred in 37% of the latter. For the first time, we propose the criteria for adrenaline autoinjector prescription for patients with typical ColdU.Abbreviations: ColdA, cold‐induced anaphylaxis; COLD‐CE, comprehensive evaluation of cold urticaria and other cold‐induced reactions, a study of the GA2LEN UCARE network; ColdU, cold urticaria; CST, cold stimulation testing; UCAREs, Urticaria Centers of Reference and Excellence
Background
Chronic urticaria (CU) predominantly affects women, and sex hormones can modulate disease activity in female CU patients. As of now, the impact of pregnancy on CU is largely unknown.
Aim
...To analyze the course and features of CU during and after pregnancy.
Patients and methods
PREG‐CU is an international, multicenter study of the Urticaria Centers of Reference and Excellence (UCARE) network. Data were collected via a 47‐item questionnaire completed by CU patients, who became pregnant within the last 3 years.
Results
A total of 288 pregnancies of 288 CU patients from 13 countries were analyzed (mean age at pregnancy: 32.1 ± 6.1 years, duration of CU: 84.9 ± 74.5 months; CSU 66.9%, CSU + CIndU 20.3%, CIndU 12.8%).During pregnancy, 51.1% of patients rated their CU as improved, 28.9% as worse, and 20.0% as unchanged.CU exacerbations most commonly occurred exclusively during the third trimester (in 34 of 124 patients; 27.6%) or the first (28 of 124; 22.8%). The risk factors for worsening of CU during pregnancy were having mild disease and no angioedema before pregnancy, not taking treatment before pregnancy, CIndU, CU worsening during a previous pregnancy, treatment during pregnancy, and stress as a driver of exacerbations. After giving birth, urticaria disease activity remained unchanged in 43.8% of CU patients, whereas 37.4% and 18.1% experienced worsening and improvement, respectively.
Conclusions
These results demonstrate the complex impact of pregnancy on the course of CU and help to better counsel patients who want to become pregnant and to manage CU during pregnancy.
During pregnancy, 51.1% of patients rated their CU as improved, 28.9% as worse, and 20.0% as unchanged; rate of angioedema decreased from 38.2% to 17.4%. CU exacerbations occurred most commonly in the third trimester (27.6%) or in the first trimester (22.8%). Of the patients whose urticaria improved during pregnancy, 50% experienced worsening after giving birth, whereas 33.6% and 16.4% reported no change. Abbreviations: CIndU, chronic inducible urticaria; CU, chronic urticaria; PREG‐CU, Pregnancy and Chronic Urticaria; UCARE, Urticaria Centers of Reference and Excellence
Background
Food anaphylaxis is commonly elicited by unintentional ingestion of foods containing the allergen above the tolerance threshold level of the individual. While labeling the 14 main ...allergens used as ingredients in food products is mandatory in the EU, there is no legal definition of declaring potential contaminants. Precautionary allergen labeling such as “may contain traces of” is often used. However, this is unsatisfactory for consumers as they get no information if the contamination is below their personal threshold. In discussions with the food industry and technologists, it was suggested to use a voluntary declaration indicating that all declared contaminants are below a threshold of 0.5 mg protein per 100 g of food. This concentration is known to be below the threshold of most patients, and it can be technically guaranteed in most food production. However, it was also important to assess that in case of accidental ingestion of contaminants below this threshold by highly allergic patients, no fatal anaphylactic reaction could occur. Therefore, we performed a systematic review to assess whether a fatal reaction to 5mg of protein or less has been reported, assuming that a maximum portion size of 1kg of a processed food exceeds any meal and thus gives a sufficient safety margin.
Methods
MEDLINE and EMBASE were searched until 24 January 2021 for provocation studies and case reports in which one of the 14 major food allergens was reported to elicit fatal or life‐threatening anaphylactic reactions and assessed if these occurred below the ingestion of 5mg of protein. A Delphi process was performed to obtain an expert consensus on the results.
Results
In the 210 studies included, in our search, no reports of fatal anaphylactic reactions reported below 5 mg protein ingested were identified. However, in provocation studies and case reports, severe reactions below 5 mg were reported for the following allergens: eggs, fish, lupin, milk, nuts, peanuts, soy, and sesame seeds.
Conclusion
Based on the literature studied for this review, it can be stated that cross‐contamination of the 14 major food allergens below 0.5 mg/100 g is likely not to endanger most food allergic patients when a standard portion of food is consumed. We propose to use the statement “this product contains the named allergens in the list of ingredients, it may contain traces of other contaminations (to be named, e.g. nut) at concentrations less than 0.5 mg per 100 g of this product” for a voluntary declaration on processed food packages. This level of avoidance of cross‐contaminations can be achieved technically for most processed foods, and the statement would be a clear and helpful message to the consumers. However, it is clearly acknowledged that a voluntary declaration is only a first step to a legally binding solution. For this, further research on threshold levels is encouraged.
Background
Although chronic urticaria (CU) is a common and primarily affects females, there is little data on how pregnancy interacts with the disease.
Objective
To analyse the treatment use by CU ...patients before, during and after pregnancy as well as outcomes of pregnancy.
Methods
PREG‐CU is an international, multicentre study of the Urticaria Centers of Reference and Excellence network. Data were collected via a 47‐item‐questionnaire completed by CU patients who became pregnant during their disease course.
Results
Questionnaires from 288 CU patients from 13 countries were analysed. During pregnancy, most patients (60%) used urticaria medication including standard‐dose second generation H1‐antihistamines (35.1%), first generation H1‐antihistamines (7.6%), high‐dose second‐generation H1‐antihistamines (5.6%) and omalizumab (5.6%). The preterm birth rate was 10.2%; rates were similar between patients who did and did not receive treatment during pregnancy (11.6% vs. 8.7%, respectively). Emergency referrals for CU and twin birth were risk factors for preterm birth. The caesarean delivery rate was 51.3%. More than 90% of new‐borns were healthy at birth. There was no link between any patient or disease characteristics or treatments and medical problems at birth.
Conclusion
Most CU patients used treatment during pregnancy especially second‐generation antihistamines which seem to be safe during pregnancy regardless of the trimester. The rates of preterm births and medical problems of new‐borns in CU patients were similar to population norms and not linked to treatment used during pregnancy. Emergency referrals for CU increased the risk of preterm birth and emphasize the importance of sufficient treatment to keep urticaria under control during pregnancy.
Acute invasive fungal rhinosinusitis is a lethal infectious process afflicting immunocompromised individuals. Knowledge about this disease is still limited due to the scarcity of animal models ...designed to study the pathogenesis of this infection. Mast cells are tissue-resident immune cells that participate in a variety of allergic and inflammatory conditions. Limited attention has been given to the role of mast cells in acute invasive fungal rhinosinusitis. Therefore, the objectives of this study were to create a rat model of acute invasive fungal rhinosinusitis based on analyzing the impact of different fungal concentrations on establishing infection, and to observe the changes of mast cells in rats with this disease.
Sprague-Dawley rats were divided randomly into four groups, three of which were experimental and received different concentrations of Aspergillus fumigatus inoculations, and one was a control group (D). The inoculated Aspergillus fumigatus concentrations were 5 × 10(7) conidia/ml in group A, 10(7) conidia/ml in group B, and 10(6) conidia/ml in group C. Before fungal inoculation, rats were immunosuppressed using cyclophosphamide and cortisone acetate, and had Merocel sponges inserted into the right nares. Hematology and histopathology investigations were then performed.
An acute invasive fungal rhinosinusitis rat model was established successfully with an incidence rate of 90% in group A, 50% in group B and 10% in group C. Aspergillus fumigatus invasion was observed in 20% of the lungs in group A, but was not seen in the remaining groups. In addition, no fungi invaded the orbital tissue, brains, livers, spleens or kidneys of any rat. Compared with the control set, the total number of mast cells in the experimental groups was not significantly increased, but mast cell degranulation, on the other hand, was only found in infected nasal cavities.
This investigation illustrates that various fungal concentrations have different effects on the incidence of acute invasive fungal rhinosinusitis, and it also demonstrates the feasibility of using this model to study the process of fungal rhinosinusoidal invasion. In addition, the results suggest that mast cells may play a role in the protection of sinuses against acute Aspergillus fumigatus infection and in the clearance of established hyphal masses.
PDF
