Tick exposures and alpha-gal syndrome: A systematic review of the evidence.

Alpha-gal syndrome (AGS) refers to a delayed allergic reaction to galactose-α-1,3-galactose (α-Gal) that occurs following the consumption of mammalian meat or exposure to other animal-based foods and products. Increasing evidence suggests that bites from certain tick species can lead to AGS through sensitization of a person's α-Gal specific IgE levels. This systematic review aimed to summarize the published evidence on this topic to understand post-tick exposure AGS epidemiology and health outcomes. A structured search for literature in eight bibliographic databases was conducted in January, 2020. Grey literature and verification searches were also performed. The exposure of interest was tick bites, and the outcome of interest was AGS. All primary research study designs were eligible for inclusion. References were screened for relevance, and data extraction and risk-of-bias assessment were conducted on relevant studies by two independent reviewers. Data were descriptively and narratively summarized. Of 1390 references screened, 102 relevant articles (103 unique studies) were identified (published from 2009 to 2020). Most studies (76.7 %) were case report or series. These 79 studies reported on 236 post-tick exposure AGS cases from 20 different countries, mostly the United States (33.5 %), Spain (19.5 %), Sweden (18.6 %), and France (12.7 %). The mean case age was 51.3 (SD = 16.7, range 5-85, n = 229), while 68.1 % were male (n = 226). The most commonly reported symptom was urticaria (71.2 %); 51.7 % of cases reported anaphylaxis. Twenty-one observational studies were reported, mostly (95.2 %) among clinical allergy patients. The proportion of AGS cases that recalled tick bites was highly variable across these studies. Three challenge studies evaluating tick exposures and α-Gal levels in α-Gal deficient mice were identified. The existing evidence suggests tick bites lead to α-Gal-specific IgE sensitization, which can cause AGS, but further research is needed to clarify if AGS is only attributable to certain tick species and whether other vectors may trigger AGS. Additional research is needed on risk factors for AGS development, evaluation of diagnostic immunoassays, and the epidemiology and distribution of AGS in different populations. Climate change will likely lead to future cases of AGS in new regions worldwide due to the predicted alteration of suitable tick habitats.

[Anaphylaxis due to a ruptured hydatid cyst]. / Anaphylaxie bei rupturierter Echinokokkuszyste.

HISTORY AND CLINICAL FINDINGS: We report the case of a 27-year-old Syrian patient who came to the emergency department with a syncopal episode. No medical history could be raised due to a language barrier and so the clinical presentation was leading. INVESTIGATIONS AND DIAGNOSIS: The patient exhibited signs of shock, accompanied by an exanthema as well as perioral hematin. In an ultrasound sonography free intraabdominal fluid and an obscure change in the upper abdomen could be visualized. An esophagogastroduodenoscopy showed evidence of an ulcer, however did not explain all symptoms. In a CT abdomen, signs of a ruptured cyst could be demonstrated. TREATMENT AND COURSE: The patient stabilized under the treatment protocol for anaphylaxis. Due to the clinical course and country of origin the patient received albendazole and a partial liver resection for a suspected echinococcus cyst. CONCLUSION: Obscure clinical symptoms alongside signs of shock, should always considered to be an allergic reaction in absence of sepsis or hemorrhage. In anaphylaxis, echinococcosis should always be included in the differential diagnosis.

Regulation of IgE by T follicular helper cells.

Allergies to food and environmental antigens have steeply grown to epidemic proportions. IgE antibodies are key mediators of allergic disease, including life-threatening anaphylaxis. There is now compelling evidence that one of the hallmarks of anaphylaxis-inducing IgE molecules is their high affinity for allergen, and the cellular pathway to high-affinity IgE is typically through sequential switching of IgG B cells. Further, in contrast to the previously held paradigm that a subset of CD4+ T cells called Th2 cells promotes IgE responses, recent studies suggest that T follicular helper cells are crucial for inducing anaphylactic IgE. Here we discuss recent studies that have enabled us to understand the nature, induction, and regulation of this enigmatic antibody isotype in allergic sensitization.

TLR9 agonist adsorbed to alum adjuvant prevents asthma-like responses induced by Blomia tropicalis mite extract.

Blomia tropicalis mite is highly prevalent in tropical and subtropical regions and it is associated with allergic diseases such as rhinitis and asthma. By using an OVA-model of allergic lung disease, we have previously shown that sensitization in the presence of toll like receptors (TLRs) agonists attenuates subsequent OVA-induced allergic responses. Here, we evaluated the effect of CpG-ODN, a specific synthetic TLR-9 agonist, on the development of experimental asthma induced by Blomia tropicalis extract, a relevant source of aeroallergens. Among different protocols of Blomia tropicalis extract sensitization, the subcutaneous sensitization in the presence of alum adjuvant induced the highest Th2 responses, including high IgE levels. Adsorption of CpG to Blomia tropicalis extract/Alum attenuated the airway hyperreactivity, the infiltration of inflammatory cells including eosinophils, and the IL-5 content in BAL. In addition, lung peribronchial inflammatory infiltrate, mucus production and IL-5-producing CD3+ CD4+ T cells were significantly reduced in the Blomia tropicalis extract/Alum+CpG group. Importantly, CpG inhibited total IgE production as well as active systemic or cutaneous anaphylaxis reactions. Inhibition of pulmonary Th2 responses was associated with increased IL-10 production but not with IFN-γ production. Notably, in IL-10-deficient mice, sensitization with OVA/Alum+CpG resulted in intense lung neutrophilia and IFN-γ production, indicating that IL-10 is necessary to inhibit subsequent Th1 immunity. Our work highlights the mechanisms of allergy attenuation by CpG and it indicates the potential use of Alum-based formulation with CpG to treat allergic processes.

Delayed hypersensitivity reaction to mammalian galactose-α-1,3-galactose (α-Gal) after repeated tick bites in a patient from France.

The α-Gal syndrome is a tick-associated and emerging IgE-mediated hypersensitivity reaction directed against the carbohydrate Galα1-3Galß1-(3)4GlcNAc-R (α-Gal) epitope after red meat intake. Herein, we describe a clinical case of a 44-year-old French patient who suffered from recurrent anaphylactic reactions after mammalian meat consumption for five years before the final diagnosis of the α-Gal syndrome was established in 2018. The patient also reported multiple tick bites prior to symptom onset. This unique type of allergy has increasingly been reported across the world, but it is still unknown in many European countries. Therefore, the present clinical case should increase awareness among primary care practitioners and further improve the early diagnosis of the α-Gal syndrome in affected individuals.

[Oral anaphylaxis by ingestion of mites contaminated oats in Panama City]. / Anafilaxia oral por ingestión de avena contaminada por ácaros en la ciudad de Panamá.

BACKGROUND: Oral anaphylaxis due to food intake contaminated with mites (OMA, oral mite anaphylaxis) is an allergic reaction that can represent life risk for patients. There are reports of cases from different parts of the world and they involve mainly processed foods based on wheat flour contaminated with mites of several families of the Astigmatina cohort. However, it remains as a little known and difficult to diagnose syndrome. The objective of this study was to describe the first clinical case of OMA due to the consumption of oat flakes in Panama City, Panama. CLINICAL CASE: Female patient of 39-years-old was entered an emergency room with allergic cutaneous and respiratory symptoms one hour after ingesting granola and oatmeal with milk at breakfast. After antiallergic treatment, the cause of allergy was determined by applying skin prick tests for ingested food and house mites. Results indicated a negative reaction for food and positive for mites. The mite analysis of the food samples directed in the identification of the species Blattisocius keegani and Suidasia pontifica, with a high density of the latter in flaked oats. CONCLUSION: This work is the first worldwide report of anaphylaxis due to consumption of oats contaminated with mites.

Antecedentes: La anafilaxia oral por ingesta de alimentos contaminados con ácaros (OMA) es una reacción alérgica que puede representar riesgo de vida para los pacientes. Aun cuando se tienen reportes de casos de diversas partes del mundo que involucran principalmente alimentos elaborados con harina de trigo contaminada con ácaros de varias familias de la cohorte Astigmatina, OMA permanece como un síndrome poco conocido y de difícil diagnóstico. El objetivo del estudio fue describir el primer caso de OMA por consumo de avena en hojuelas ocurrido en la ciudad de Panamá, Panamá. Caso clínico: Mujer de 39 años que ingresó a urgencias de un hospital con cuadro alérgico cutáneo y respiratorio una hora después de ingerir granola y avena con leche en el desayuno. Después del tratamiento antialérgico se procedió a determinar la causa de la alergia mediante aplicación de pruebas de punción cutánea para los alimentos ingeridos y ácaros domésticos. Los resultados indicaron reacción negativa para alimentos y positiva para ácaros. El análisis acarológico de las muestras de alimentos resultaron en la identificación de las especies Blattisocius keegani y Suidasia pontifica, con alta densidad de la última en la muestra de avena. Conclusiones: El presente reporte constituye el primero en el mundo de anafilaxia por consumo de avena contaminada con ácaros.

Tick-induced allergies: mammalian meat allergy and tick anaphylaxis.

Mammalian meat allergy after tick bites and tick anaphylaxis are the most serious tick-induced allergies. They are often severe, should be largely avoidable and offer fascinating insights into the development and prevention of allergies. Australian clinicians reported the first cases of tick anaphylaxis and discovered the association between tick bites and the development of mammalian meat allergy. The subsequent finding of the allergen epitope within the meat responsible for the allergic reaction, α-gal (galactose-α-1,3-galactose), stimulated further interest in this emergent allergy. Reports of mammalian meat allergy associated with bites from several tick species have now come from every continent where humans are bitten by ticks. The number of diagnosed patients has continued to rise. Clinically, mammalian meat allergy and tick anaphylaxis present quite differently. The prominent role of cofactors in triggering episodes of mammalian meat allergy can make its diagnosis difficult. Management of mammalian meat allergy is complicated by the manifold potential therapeutic implications due to the widespread distribution of the mammalian meat allergen, α-gal. Exposures to α-gal-containing medications have proved lethal in a minority of people, and fatal tick anaphylaxis has been reported in Australia. Prevention of tick bites is prudent and practicable; killing the tick in situ is crucial to both primary and secondary prevention of allergic reactions. Mechanisms in the development of mammalian meat allergy constitute a paradigm for how allergies might arise.

Identification of IgE and IgG1 specific antigens in Echinococcus granulosus cyst fluid.

Cystic echinococcosis (CE) is an anthropozoonotic disease with worldwide distribution and is caused by the cestode Echinococcus granulosus. Anaphylactic shock induced by CE rupture is a serious complication especially in patients with hydatid infections, as the resulting leakage of fluid contains highly toxic endogenous antigen. We aimed to isolate and identify the antigens of specific IgE and IgG1 (sIgE and sIgG1) in E. granulosus cyst fluid (EgCF). Crude antigen for EgCF was prepared from E. granulosus-infected sheep liver. Antigens were separated and identified by one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (1D SDS-PAGE), two-dimensional gel electrophoresis (2-DE), and immunoblotting. Results of 1D SDS-PAGE and immunoblotting showed that 40.5 kDa protein was the major antigen of sIgE, and 35.5 kDa protein was the major antigen of sIgG1 in EgCF. Results of 2-DE and immunoblotting showed that main antigens of sIgE in EgCF were four proteins with pI values ranging from 6.5 to 9.0 and a molecular weight of 40.5 kDa. Main antigens of sIgG1 in EgCF were five proteins with pI values ranging from 6.5 to 9.0 and a molecular weight of 35.5 kDa. The antigens identified for sIgE and sIgG1 can provide critical insights into cellular and molecular mechanisms underlying anaphylactic shock induced by CE.

Identification of IgE and IgG1 specific antigens in Echinococcus granulosus cyst fluid

Cystic echinococcosis (CE) is an anthropozoonotic disease with worldwide distribution and is caused by the cestode Echinococcus granulosus. Anaphylactic shock induced by CE rupture is a serious complication especially in patients with hydatid infections, as the resulting leakage of fluid contains highly toxic endogenous antigen. We aimed to isolate and identify the antigens of specific IgE and IgG1 (sIgE and sIgG1) in E. granulosus cyst fluid (EgCF). Crude antigen for EgCF was prepared from E. granulosus-infected sheep liver. Antigens were separated and identified by one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (1D SDS-PAGE), two-dimensional gel electrophoresis (2-DE), and immunoblotting. Results of 1D SDS-PAGE and immunoblotting showed that 40.5 kDa protein was the major antigen of sIgE, and 35.5 kDa protein was the major antigen of sIgG1 in EgCF. Results of 2-DE and immunoblotting showed that main antigens of sIgE in EgCF were four proteins with pI values ranging from 6.5 to 9.0 and a molecular weight of 40.5 kDa. Main antigens of sIgG1 in EgCF were five proteins with pI values ranging from 6.5 to 9.0 and a molecular weight of 35.5 kDa. The antigens identified for sIgE and sIgG1 can provide critical insights into cellular and molecular mechanisms underlying anaphylactic shock induced by CE.

Dexamethasone attenuates echinococcosis-induced allergic reactions via regulatory T cells in mice.

BACKGROUND: Cystic echinococcosis (CE), caused by infection with Echinococcus granulosus larvae, is a potentially life-threatening disease in humans. Anaphylactic shock caused by CE is very dangerous, and is highly prevalent during surgery. Dexamethasone (DEX) is used clinically before operations to prevent allergic reactions; Regulatory T cells (Treg cells) are believed to be associated with negative immune response, which play an important role in alleviating allergic reactions. However, the association of Treg cells with DEX remains unknown. METHODS: In this study, C57BL/6 mice were divided into uninfected group, untreated group and DEX group which were inoculated with protoscoleces from E. granulosus and sensitized using a cyst fluid suspension to induce anaphylactic shock. In addition, the mice in DEX group were treated with 10 mg/kg DEX by intraperitoneal injection 30 min before being sensitized. RESULTS: It was found that 93.75 % of all sensitized mice experienced allergic symptoms. The levels of IgE, IgE/IgG, and IgE/IgG1 were significantly higher in both untreated group and DEX group. The proportion of CD4 + CD25 + FOXP3 + Treg cells relative to CD4+ Treg cells, and the levels of interleukin-10 (IL-10) and tumor growth factor-ß (TGF-ß1) were significantly higher in DEX group. The level of IL-13 was significantly higher in the sensitized mice than in the other groups. These cells may play a key role in alleviating the immune response in CE-induced anaphylactic shock. CONCLUSIONS: The protective effect of DEX may be due to Treg cell upregulating IL-10 and TGF-ß1 levels, and inhibiting helper T cell 2 cytokines.

Spontaneous rupture of a splenic hydatid cyst with anaphylaxis in a patient with multi-organ hydatid disease.

Hidatid cysts of the spleen are a rare occurrence, the spleen being the third most common organ for the development of Echinococcus Granulosus. Splenic hydatid cysts are commonly part of multi-organ hydatid disease. Diagnosis is often established when investigating a splenomegaly or by chance during an unrelated consult. It can also be diagnosed after rupture, be it following trauma (the most common occurrence)or spontaneous. Splenic hydatid cyst rupture requires immediate action and is a life-threatening condition. It results, most often, in splenectomy. We present the case of a patient with multi-organ hydatid disease that presented with a ruptured splenic cyst and developed anaphylaxis. The case was resolved by splenectomy and recovered well.

[IL-10 level in allergic rats infected by Echinococcus granulosus].

Forty Wistar rats were randomly divided into 4 groups with 10 in each group. Group A served as normal control. The other 3 groups were injected intraperitoneally with Echinococcus granulosus protoscoleces 5 x 10(4) each. Six months later, group D was injected intraperitoneally with antibody against IL-10 2.0 microg/time, twice a day for 2 d. Two days later, rats in groups C and D were injected intraperitoneally with cyst fluid 5 ml each to induce allergic reaction. 30 min later, all the rats were sacrificed to observe the infection status and obtain peripheral blood. The level of IL-10, IgE and histamine in the sera was detected by ELISA. The results showed that 5, 6 and 5 rats in groups B, C and D were infected successfully, respectively, with 2 deaths in group A. The rats in groups C and D appeared nasal itching, sneezing and declined activity. 30 min later, the symptoms in group C got improved, but not for group D. The levels of IL-10 and IgE in groups C and D increased significantly compared to group B (P < 0.05). The levels of IL-10 and IgE in group D were (142.61 +/- 43.58) pg/ml and (20.67 +/- 1.58) microg/ml, respectively, lower than those in group C (P < 0.05). The level of histamine was (17.69 +/- 3.90) ng/ml, higher than that in groups B and C (P < 0.05). There was no significant difference in histamine level between B and C (P > 0.05).

[A mortal cause of syncope]. / Una causa mortal de síncope.

Anaphylaxis is a generalized reaction produced by the massive release of mediators from mast cells, is rapid in onset and may cause death. The diagnosis is clinical, and the initial symptoms often overlap with those of many other disorders such as, vasovagal reactions, anxiety or asthma, and is often underdiagnosed. A high index of suspicion is necessary for the diagnosis. We report the case of a young woman who presented with syncope in a Primary Care Centre. In spite of the absence of skin lesions, we suspected an anaphylaxis because of the refractory low blood pressure. Thus treatment was started she was transferred to the Hospital. In the Emergency Department, the elevated serum tryptase levels supported our diagnosis. The absence of a clear exposure to a known allergen lead us to suspect a hydatid cysts rupture. The abdominal ultrasound and CT scan confirmed this.

The Anisakis allergy debate: does an evolutionary approach help?

Allergic phenomena share common pathways with the immune response against helminth parasites. The definitions regarding allergens and their related concepts have their roots in the area of allergy research. The experience with the fish parasite Anisakis simplex-associated allergic features still nurtures an open debate on the necessity of larvae being alive to induce allergic reactions such as urticaria or anaphylaxis. Conceptual definitions of allergen, major allergen, as well as putatively crossreacting antibodies, as are used in food allergy, depend on the clinical relevance of specific IgE and deserve careful interpretation in the various forms of A. simplex-associated allergic features. Conversely, an evolutionary based interpretation of the presence of specific IgE depends on the viability of A. simplex.