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.

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).

Anisakis simplex-induced anaphylaxis.

In recent years, Anisakis simplex has been shown to be an important etiologic agent responsible for food allergy and for gastrointestinal anisakiasis. We report a 61-year-old woman presenting with generalized urticaria and subsequent anaphylaxis after ingestion of raw mackerel. She rapidly recovered with administration of epinephrine and endoscopic extraction of an A. simplex larva. Serologic testing revealed specific IgE antibody to A. simplex was positive whereas that to mackerel was negative. She was diagnosed as IgE-mediated hypersensitivity to A. simplex. Patients diagnosed as fish-related or idiopathic allergy should be examined for evidence of Anisakis-induced allergy.

Ruptured pulmonary hydatid cyst with anaphylactic shock and pneumothorax.

Hydatid cyst is a disease caused by a parasitic tapeworm, Echinococcus granulosus, and most commonly involves liver and lung. Ruptured pulmonary hydatid cyst can present a diagnostic challenge, and radiograph can be inconclusive. Anaphylactic reaction is a rare complication of ruptured pulmonary hydatid cyst. A 22-year-old male came to our emergency department in shock with symptoms of shortness of breath and altered mental status from the previous day. Radiograph showed a thin-walled circular translucent area in the right upper lung field, which was misdiagnosed as pneumothorax, and an intercostal chest tube was inserted. After 5 days, repeat radiograph revealed a cavity with an air/fluid level. The chest tube was removed and contrast-enhanced computed tomogram showed a cavity with water-lily sign, which suggests ruptured hydatid cyst. Immunoglobin-G enzyme-linked immunosorbent assay for Echinococcus was positive. The patient responded well to treatment with crystalloid infusion, supplemental oxygen, and albendazole, and then underwent surgery. Anaphylactic reaction due to rupture of a hydatid cyst is rare, but hydatid disease should be suspected in patients from areas where Echinococcus is endemic.

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.

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.

[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.

Ruptured hydatid cyst in a patient with shock.

Echinococcosis is a severe helminthic zoonosis largely caused by Echinococcus granulosus and frequently encountered in endemic areas. The liver and lung are the most frequently involved organs. Cyst rupture into the peritoneal cavity represents a rare but serious complication. Herein, we describe an acute occurrence of anaphylactic shock due to a spontaneous rupture of hydatid cyst in a 21-year-old Turkish patient unwittingly infected by Echinococcosis. Resection surgery of the perforated cyst in combination with cleaning of the abdominal cavity was performed. The patient rapidly improved and no relapse occurred during a follow-up of 8 months. Anaphylaxis is a serious complication of hydatid cyst rupture and needs to be promptly diagnosed. The main objective of our report is to underscore this life-threatening complication that should be considered when anaphylactic shock of unknown origin occurs, even in non-endemic regions. Moreover, we emphasize the need for a radical surgical approach to avoid widespread dissemination.

[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.

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.

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.

Recurrent anaphylaxis due to non-ruptured hepatic hydatid cysts.

BACKGROUND: Hydatid disease, a parasitic infestation of humans, is endemic in the Mediterranean region, Australia, New Zealand and the Middle East, and mostly involves the liver. Anaphylactic reactions, which sometimes are the first manifestations of the disease, frequently occur due to cyst rupture after a minor/major trauma, though they may also be spontaneously seen on rare occasions. In extremely few studies, anaphylactic shock has been reported in patients without macroscopic rupture of the hydatid cysts. CASE REPORT: Our patient had recurrent anaphylactic episodes without any trauma and had been misdiagnosed for several years even though the patient was living in a region endemic for hydatid disease. CONCLUSION: We emphasize that physicians should be highly aware of hydatid disease as a possible etiology for seemingly idiopathic anaphylactic reactions, especially in endemic regions.

[New data on anisakiasis]. / Données nouvelles sur l'anisakidose.

Acute anisakiasis is generally due to the third-stage larvae of Anisakis simplex, and occasionally to other anisakidae. Human infection occurs through consumption of raw seafish, and especially herring, hake, black plaice and cod. Patients sensitized by prior consumption of parasitized fish develop, within a few hours, violent abdominal pain and an allergic reaction. Anisakis-induced urticaria is seen in about one in five cases. Preventive measures have reduced the number of cases. In France for example, the number of cases fell four-fold between 1977-1991 and 1992-2005. In 1990 Kasuya [1] reported chronic anisakiasis related to consumption of cooked parasitized fish. Seafish-induced urticaria might be an allergic response to Anisakis larval antigens rather than to the fish itself. Indeed, 11 patients with mackerel-related urticaria all had a positive reaction to Anisakis simplex larval antigen, while none reacted to mackerel antigen. A low-molecular-weight thermostable A. simplex allergen causes chronic urticaria, angioedema and even anaphylactoid reactions. Victims have a genetic predisposition (HLA class II alleles) that is uncommon in France and Germany but frequent in Japan. A number of cases have been observed in Spain, where fish is particularly popular. Immunoblotting shows cross-reactions between antigens of A. simplex and Toxocara canis, nematodes belonging to the same superfamily. At present, the only way to avoid contracting anisakiasis is not to eat raw or even cooked parasitized seafish.

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.

Lack of active lung anaphylaxis in congenitally mast cell-deficient Ws/Ws rats sensitized with the nematode Nippostrongylus brasiliensis.

Ws/Ws rats are deficient in both mucosal- and connective tissue-type mast cells. To study the role of mast cells in active anaphylaxis, changes in vascular permeability in the trachea upon intravenous antigen challenge with Evans blue dye were examined in Ws/Ws, heterogenic Ws/+, and normal +/ + rats sensitized with the nematode Nippostrongylus brasiliensis. Antigen challenge resulted in fatal anaphylactic shock in some +/+ and Ws/+ rats, but not in Ws/Ws rats. Marked dye leakage developed within 30 min in the trachea of +/+ and Ws/+ rats, while Ws/Ws rats showed no substantial increases in the levels of vascular permeability. Ex vivo stimulation of sensitized lung fragments from +/+ animals with specific antigen induced significant releases of histamine and leukotriene (LT) C4, while sensitized Ws/Ws rat-lung fragments did not. In Ws/Ws rats, levels of nematode-specific IgE, IgG1 and IgG2a antibodies as well as levels of lung eosinophilia were not significantly different from those in +/+ rats. These results show that mast cell-deficient Ws/Ws rats fail to develop active anaphylaxis, and this is mediated probably by the lack of mast cell-derived mediators required for initiation of the reaction.