Abstract The risk of hematological malignancies is mainly determined by genetic background, age, sex, race and ethnicity, geographic location, exposure to certain chemicals and radiation; along with ...the more recently proposed immune factors such as chronic inflammation, immunodeficiencies, autoimmunity, and infections. Paradigmatic examples include the development of lymphoma in Sjögren's syndrome and Hashimoto thyroiditis, gastric MALT lymphoma in Helicobacter pylori infection, or lymphomas associated with infections by Epstein–Barr virus, human herpes virus 8 (HHV 8) and leukemia/lymphoma virus 1 (HTLV-1). A growing number of reports indicates an increased risk of lymphoma, particularly of the anaplastic large cell (ALCL) type. The implants, specifically those used in the past, elicit chronic stimulation of the immune system against the prosthetic material. This is particularly the case in genetically susceptible hosts. We suggest that polyclonal activation may result in monoclonality in those at risk hosts, ultimately leading to lymphoma. We suggest that patients with an inflammatory response against silicone implants be monitored carefully.
Mast cell-activating signals in cold urticaria are not yet well defined and are likely to be heterogeneous. Cold agglutinins and cryoglobulins have been described as factors possibly associated with ...cold urticaria, but their relevance has not been explained. We performed a single-center prospective cohort study of 35 cold urticaria patients. Cold agglutinin and cryoglobulin test results, demographics, detailed history data, cold stimulation test results, complete blood count values, C-reactive protein, total immunoglobulin E levels, and basal serum tryptase levels were analyzed. Forty six percent (
= 16) of 35 tested patients had a positive cold agglutinin test and 27% (
= 9) of 33 tested patients had a positive cryoglobulin test. Cold agglutinin positive patients, when compared to cold agglutinin negative ones, were mainly female (
= 0.030). No gender-association was found for cryoglobulins. A positive cold agglutinin test, but not a positive cryoglobulin test, was associated with a higher rate of reactions triggered by cold ambient air (
= 0.009) or immersion in cold water (
= 0.041), and aggravated by increased summer humidity (
= 0.007). Additionally, patients with a positive cold agglutinin test had a higher frequency of angioedema triggered by ingestion of cold foods or drinks (
= 0.043), and lower disease control based on Urticaria Control Test (
= 0.023). Cold agglutinin levels correlated with erythrocyte counts (r = -0.372,
= 0.028) and monocyte counts (r = -0.425,
= 0.011). Cryoglobulin concentrations correlated with basal serum tryptase levels (r = 0.733,
= 0.025) and cold urticaria duration (r = 0.683,
= 0.042). Results of our study suggest that cold agglutinins and cryoglobulins, in a subpopulation of cold urticaria patients, are linked to the course and possibly the pathogenesis of their disease.
A 20-year-old man developed severe abdominal pain 1 week after being vaccinated with the first dose of quadrivalent human papillomavirus (HPV) vaccine (Gardasil
®
). Despite ongoing symptoms of ...nausea and pain, he received the second dose of the vaccine. Only 10 days later, laboratory results revealed significantly elevated pancreatic enzymes, and with concomitant abdominal pain and vomiting, he was diagnosed with acute pancreatitis. This case of acute pancreatitis after HPV vaccination is not a novel entity. Although confirming the relationship between pancreatitis and vaccine is challenging, some factors suggest a possible link, including the positive re-challenge upon repeated exposure to the vaccine, HPV vaccine as probable causal relationship to other autoimmune diseases and a probable mechanism of molecular mimicry. In conjunction with aluminum adjuvant, the induction of immunity through molecular mimicry may potentially culminate in production of cytotoxic autoantibodies with a particular affinity for pancreatic acinar cells.
Cryoproteins, such as cryoglobulins, cryofibrinogens and cold agglutinins, precipitate at low temperatures or agglutinate erythrocytes and dissolve again when warmed. Their pathogenetic and ...diagnostic importance in cold urticaria (ColdU) is unclear. In this study, we aimed to characterize the prevalence of cryoproteins in patients with ColdU.
We conducted 3 analyses: i) a systematic review and meta-analysis of published data using an adapted version of the Joanna Briggs Institute's critical appraisal tool for case series, ii) a retrospective analysis of 293 ColdU patients treated at our Urticaria Center of Reference and Excellence (UCARE) from 2014 to 2019, and iii) a prospective observational study, from July 2019 to July 2020, with 49 ColdU patients as defined by the EAACI/GA2LEN/EDF/UNEV consensus recommendations.
Our systematic review identified 14 relevant studies with a total of 1151 ColdU patients. The meta-analyses showed that 3.0% (19/628), 1.1% (4/357) and 0.7% (2/283) of patients had elevated levels of cryoglobulins, cryofibrinogens and cold agglutinins, respectively. Our retrospective analyses showed that cryoproteins were assessed in 4.1% (12/293) of ColdU patients. None of 9 ColdU patients had cryoglobulins, and one of 5 had cold agglutinins. In our prospective study, none of our patients had detectable cryoglobulins (0/48) or cryofibrinogens (0/48), but 4.3% (2/46) of patients had cold agglutinins (without any known underlying autoimmune or hematological disorder).
Our investigation suggests that only very few ColdU patients exhibit cryoproteins and that the pathogenesis of ColdU is driven by other mechanisms, which remain to be identified and characterized in detail.
The relationship between anti-SARS-CoV-2 humoral immune response, pathogenic inflammation, lymphocytes and fatal COVID-19 is poorly understood.
A longitudinal prospective cohort of hospitalised ...patients with COVID-19 (n=254) was followed up to 35 days after admission (median, 8 days). We measured early anti-SARS-CoV-2 S1 antibody IgG levels and dynamic (698 samples) of quantitative circulating T-, B- and natural killer lymphocyte subsets and serum interleukin-6 (IL-6) response. We used machine learning to identify patterns of the immune response and related these patterns to the primary outcome of 28-day mortality in analyses adjusted for clinical severity factors.
Overall, 45 (18%) patients died within 28 days after hospitalisation. We identified six clusters representing discrete anti-SARS-CoV-2 immunophenotypes. Clusters differed considerably in COVID-19 survival. Two clusters, the anti-S1-IgG
T
B
NK
IL-6
and the anti-S1-IgG
T
B
NK
IL-6
had a high risk of fatal COVID-19 (HR 3.36-21.69; 95% CI 1.51-163.61 and HR 8.39-10.79; 95% CI 1.20-82.67; p≤0.03, respectively). The anti-S1-IgG
T
B
NK
IL-6
and anti-S1-IgG
T
B
NK
IL-6
cluster were associated with moderate risk of mortality. In contrast, two clusters the anti-S1-IgG
T
B
NK
IL-6
and anti-S1-IgG
T
B
NK
IL-6
clusters were characterised by a very low risk of mortality.
By employing unsupervised machine learning we identified multiple anti-SARS-CoV-2 immune response clusters and observed major differences in COVID-19 mortality between these clusters. Two discrete immune pathways may lead to fatal COVID-19. One is driven by impaired or delayed antiviral humoral immunity, independently of hyper-inflammation, and the other may arise through excessive IL-6-mediated host inflammation response, independently of the protective humoral response. Those observations could be explored further for application in clinical practice.
Purpose of review
Cold-induced anaphylaxis (ColdA) is a poorly understood form of anaphylaxis that occurs in patients with cold urticaria (ColdU). This comprehensive review aims to deepen the ...understanding of ColdA. It emphasizes the identification of high-risk ColdU patients susceptible to ColdA and provides recommendations for their effective management.
Recent findings
Recent studies, including the large international COLD-CE study, have identified clinical features of ColdU patients associated with increased ColdA risk. These individuals can now be recognized through routine clinical assessments. Key diagnostic indicators for assessing ColdU and the risk of ColdA include oropharyngeal/laryngeal symptoms and positive standard local cold provocation tests. ColdA has been defined as acute cold-induced involvement of the skin and/or visible mucosal tissue accompanied by cardiovascular manifestations, difficulty breathing, or gastrointestinal symptoms, but a universally accepted definition is lacking. Additionally, ColdA has recently been recognized as an indication for prescribing adrenaline (epinephrine) autoinjectors, marking a significant advancement in disease management.
Summary
ColdA is a major and potentially life-threatening concern for a subset of ColdU patients. Early recognition of high-risk patients, coupled with education and preparedness of both patients and healthcare providers, is crucial for effectively managing this challenging condition. Further research is needed to expand understanding of the underlying pathophysiological mechanisms of ColdA, identify potential cofactors influencing ColdA, and improve disease-management strategies.
Cold urticaria (ColdU) is a common form of chronic inducible urticaria characterized by the development of wheals, angioedema or both in response to cold exposure. Recent research and guideline ...updates have advanced our understanding and management of ColdU. Today, its pathophysiology is thought to involve the cold‐induced formation of autoallergens and IgE to these autoallergens, which provoke a release of proinflammatory mediators from skin mast cells. The classification of ColdU includes typical and atypical subtypes. We know that cold‐induced wheals usually develop on rewarming and resolve within an hour and that anaphylaxis can occur. The diagnosis relies on the patient's history and cold stimulation testing. Additional diagnostic work‐up, including a search for underlying infections, should only be done if indicated by the patient's history. The management of ColdU includes cold avoidance, the regular use of nonsedating antihistamines and the off‐label use of omalizumab. However, many questions regarding ColdU remain unanswered. Here, we review what is known about ColdU, and we present important unanswered questions on the epidemiology, underlying pathomechanisms, clinical heterogeneity and treatment outcomes. Our aim is to guide future efforts that will close these knowledge gaps and advance the management of ColdU.
The purpose of the research was to evaluate the offer of seashell specialties in Slovene Istria restaurants, and to assess food safety knowledge (gained through formal and informal education) as well ...as to assess the behaviour of food handlers in preparing shell dishes. A self-administered questionnaire was designed that included four sections: a demographic section, a general section, a restaurant menu offer, and a food safety section related to preparation of seashell specialties. Seashell specialties were offered in 41 restaurants, of which the employed food handlers 24 attended formal education and 17 informal education. Seashells specialties and seashell menus are commonly part of the culinary and gastronomic specialties along the Slovene coast, with the most frequently offered main dish being 'Blue Mussels alla Busara'. Results the questionnaire indicated poor food safety knowledge and poor behaviour regardless of the (in)formal education of those who prepared the dishes. We propose that formal education for catering workers preparing shell dishes should be much more emphasized.
Urtikarijo zaradi hlada (UH), pri kateri se pojavijo s hladom izzvane urtike, angioedem ali oboje hkrati, delimo na tipično in atipično obliko. Diagnoza tipične UH temelji na pozitivnih lokalnih ...stimulacijskih testih (LST). Pri UH se lahko razvijejo tudi sistemske reakcije. Namen raziskave je bil določiti dejavnike tveganja za sistemske reakcije pri tipični UH. Mednarodna raziskava imenovana COLD-CE (tj. Urtikarija zaradi hlada in druge s hladom izzvane reakcije – celostno ovrednotenje) je potekala v 32 UCARE centrih (angl. Urticaria Center(s) of Reference and Excellence). Pridobili smo natančne anamnestične podatke in opravili LST s kocko ledu in/ali napravo TempTest®. Prizadetost dihal smo definirali kot dispnejo, piskanje ali stridor. Prizadetost kardiovaskularnega sistema smo definirali kot hipotenzijo ali izgubo zavesti in/ali druge simptome povezane s hipotenzijo (tj. omotica, občutek omedlevice ali nemoči). V raziskavo smo vključili 551 bolnikov z UH in 75 % od njih je imelo pozitivne LST (tj. tipično UH). Pri 40 bolnikih s tipično UH smo diagnosticirali tudi kronično spontano urtikarijo (KSU). Prizadetost dihal je nastopila pri 22 % in prizadetost kardiovaskularnega sistema pri 31 % bolnikov s tipično UH brez KSU. Ugotovili smo tri neodvisne dejavnike tveganja za prizadetost dihal: pričetek UH v otroštvu, orofaringealni in/ali laringealni simptomi ter srbež uhljev. Neodvisni dejavniki tveganja za prizadetost kardiovaskularnega sistema pa so: angioedem, orofaringealni in/ali laringealni simptomi, srbež uhljev ter predhodna sistemska reakcija na pik kožekrilca.
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