Diffuse Cutaneous Mastocytosis: A Current Understanding of a Rare Disease.

Mastocytosis is a heterogeneous disease characterized by the expansion and accumulation of neoplastic mast cells in various tissues. Diffuse cutaneous mastocytosis (DCM) is a rare and most severe form of cutaneous mastocytosis, which typically occurs in childhood. There have been reports of a familial DCM with specific gene mutations, indicating both sporadic and hereditary factors involved in its pathogenesis. DCM is associated with severe MC mediator-related symptoms and an increased risk of anaphylaxis. The diagnosis is based on the appearance of skin lesions, which typically show generalized thickening, erythroderma, blistering dermographism, and a positive Darier's sign. Recognition, particularly in infants, is challenging due to DCMs resemblance to other bullous skin disorders. Therefore, in unclear cases, a skin biopsy is crucial. Treatment focuses on symptom management, mainly including antihistamines and mast cell stabilizers. In extremely severe cases, systemic steroids, tyrosine kinase inhibitors, phototherapy, or omalizumab may be considered. Patients should be equipped with an adrenaline autoinjector. Herein, we conducted a comprehensive review of literature data on DCM since 1962, which could help to better understand both the management and prognosis of DCM, which depends on the severity of skin lesions, intensity of mediator-related symptoms, presence of anaphylaxis, and treatment response.

Snail-induced anaphylaxis in patients with underlying Artemisia vulgaris pollinosis: the role of carbohydrates.

PURPOSE: The importance of carbohydrates in anaphylaxis has been described with some foods. The current work intends to obtain clinical and immunological evidence of the importance of the O-glycans for IgE binding activity in anaphylactic reactions due to Helix aspersa (HA) ingestión and Artemisia vulgaris (AV) exposition. METHODS: The studio focused on two cases of IgE-mediated anaphylaxis induced by snail ingestion in patients with underlying rhino-conjunctivitis and asthma due to AV. We performed on both patients: skin prick tests ( SPTs) with HA and AV and with a battery of aeroallergen, controlled nasal challenge and specific IgE to HA and AV, ImmunoCAP ISAC®, and a differential pattern of IgE recognition with SDS-PAGE Immunoblotting (SDSI) when these allergens have suffered an O-deglycosylation procedure. RESULTS: The patients showed positive results in SPTs, nasal challenges, and serum-specific IgE against HA and AV. In patient 1, the SDSI detected several IgE-binding proteins in AV with a molecular mass of 22, 24, and 44 kDa, whereas a band of 12 kDa was detected in HA. On the other hand, patient 2's serum revealed an IgE-binding zone between 75 and 20 kDa in the AV and a band of 24 kDa in the HA. When glycans were removed, patient 1's serum only revealed the AV's 22 and 24 kDa bands, whereas patient 2's serum did not detect any IgE-reactive protein in the HA. CONCLUSIONS: Our data suggest that O-glycosylation can be relevant in patients with anaphylaxis due to snails and allergy to Artemisia vulgaris. This new entity representing cross-reactivity between AV and HA could be named Snail-Artemisia Syndrome.

Dupilumab for Treatment of Food-Dependent, Exercise-Induced Anaphylaxis: Report of One Case.

Food-dependent, exercise-induced anaphylaxis (FDEIA) is a potentially life-threatening disorder that often occurs with exercise, and patients typically have eaten a specific food within hours before disease onset. This disease is exceedingly rare, with a prevalence of 0.02%. No well-recognized prevention or treatment strategy has been available for FDEIA except avoiding triggers strictly. Here we report an 11-year-old boy with a history of recurrent anaphylaxis of unknown etiology more than 10 times within two years. As the anaphylactic symptoms had not been controlled after traditional treatments, the patient was given subcutaneous injection of dupilumab seven times within 33 weeks. During dupilumab treatments, the patient was exposed to culprit mushrooms plus exercises at least twice a month but without notable anaphylaxis. Thus, Dupilumab may improve the allergic reactions in FDEIA patients.

Clinacanthus nutans aqueous leaves extract exerts anti-allergic activity in preclinical anaphylactic models via alternative IgG pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Allergy is mediated by the crosslinking of immunoglobulins (Ig) -E or -G to their respective receptors, which degranulates mast cells, macrophages, basophils, or neutrophils, releasing allergy-causing mediators. The removal of these mediators such as histamine, platelet-activating factor (PAF) and interleukins (ILs) released by effector cells will alleviate allergy. Clinacanthus nutans (C. nutans), an herbal plant in Southeast Asia, is used traditionally to treat skin rash, an allergic symptom. Previously, we have reported that C. nutans aqueous leaves extract (CNAE) was able to suppress the release of ß-hexosaminidase and histamine but not interleukin-4 (IL-4) and tumor necrosis factor-alpha (TNF-α) in the IgE-induced mast cell degranulation model at 5 mg/mL and above. We also found that CNAE could protect rats against ovalbumin-challenged active systemic anaphylaxis (OVA-ASA) through the downregulation and upregulation of certain metabolites using proton nuclear magnetic resonance (1H-NMR) metabolomics approach. AIM OF THE STUDY: As allergy could be mediated by both IgE and IgG, we further evaluated the anti-allergy potential of CNAE in both in vitro model of IgG-induced macrophage activation and in vivo anaphylaxis models to further dissect the mechanism of action underlying the anti-allergic properties of CNAE. MATERIAL & METHODS: The anti-allergy potential of CNAE was evaluated in in vivo anaphylaxis models of ovalbumin-challenged active systemic anaphylaxis (OVA-ASA) and IgE-challenged passive systemic anaphylaxis (PSA) using Sprague Dawley rats as well as IgG-challenged passive systemic anaphylaxis (IgG-PSA) using C57BL/6 mice. Meanwhile, in vitro model of IgG-induced macrophage activation model was performed using IC-21 macrophages. The release of soluble mediators from both IgE and IgG-mediated pathways were measured using enzyme-linked immunosorbent assay (ELISA). The signaling molecules targeted by CNAE were identified by performing Western blot. RESULTS: IgG, platelet-activating factor (PAF) and IL-6 was suppressed by CNAE in OVA-ASA, but not IgE. In addition, CNAE significantly suppressed PAF and IL-6 in IgG-PSA but did not suppress histamine, IL-4 and leukotrienes C4 (LTC4) in IgE-PSA. CNAE also inhibited IL-6 and TNF-α by inhibiting the phosphorylation of ERK1/2 in the IgG-induced macrophage activation model. CONCLUSION: Overall, our findings supported that CNAE exerts its anti-allergic properties by suppressing the IgG pathway and its mediators by inhibiting ERK1/2 phosphorylation, thus providing scientific evidence supporting its traditional use in managing allergy.

Evaluation of emotional, Behavioral, and clinical characteristics of children aged 1-5 with a history of food-related anaphylaxis.

BACKGROUND: Our study aimed to investigate emotional, behavioral, and social characteristics assessed with internationally validated psychometric scales and their relationship with demographic, clinical, and laboratory data in children with a history of food-related anaphylaxis. METHOD: The study included patients aged 1-5 who were followed up in the pediatric allergy outpatient clinic with a diagnosis of food-related anaphylaxis. All participants were evaluated during admission to the clinic using a study questionnaire, which was prepared by the authors, consisting of three parts: a sociodemographic information form, a clinical evaluation form, and the Aberrant Behavior Checklist (ABC) for psychiatric evaluation. Parents answered the questionnaires regarding the patients' emotional and behavioral health. RESULTS: Thirty patients aged between 12 and 62 months were included in the study. The data were compared with 30 healthy controls with similar age and gender distribution. The total ABC score (p = 0.015), and the stereotypic behavior (p = 0.003) and hyperactivity (p = 0.002) subscale scores were significantly higher in patients with anaphylaxis history compared to the controls. CONCLUSION: Emotional and behavioral status assessments and the clinical follow-up of food allergies of patients who experienced anaphylaxis in early childhood are useful for the holistic management and early recognition of possible pathologies.

Dupilumab for Treatment of Food-Dependent, Exercise-Induced Anaphylaxis: Report of One Case / 中国医学科学杂志(英文版)

Food-dependent, exercise-induced anaphylaxis (FDEIA) is a potentially life-threatening disorder that often occurs with exercise, and patients typically have eaten a specific food within hours before disease onset. This disease is exceedingly rare, with a prevalence of 0.02%. No well-recognized prevention or treatment strategy has been available for FDEIA except avoiding triggers strictly. Here we report an 11-year-old boy with a history of recurrent anaphylaxis of unknown etiology more than 10 times within two years. As the anaphylactic symptoms had not been controlled after traditional treatments, the patient was given subcutaneous injection of dupilumab seven times within 33 weeks. During dupilumab treatments, the patient was exposed to culprit mushrooms plus exercises at least twice a month but without notable anaphylaxis. Thus, Dupilumab may improve the allergic reactions in FDEIA patients.

Structural and Immunologic Properties of the Major Soybean Allergen Gly m 4 Causing Anaphylaxis.

Gly m 4 is the major soybean allergen, causing birch pollen cross allergic reactions. In some cases, Gly m 4-mediated anaphylaxis takes place, but the causative factors are still unknown. Here, we studied the structural and immunologic properties of Gly m 4 to shed light on this phenomenon. We showed that Gly m 4 retained its structure and IgE-binding capacity after heating. Gly m 4 was cleaved slowly under nonoptimal gastric conditions mimicking duodenal digestion, and IgE from the sera of allergic patients interacted with the intact allergen rather than with its proteolytic fragments. Similar peptide clusters of Bet v 1 and Gly m 4 were formed during allergen endolysosomal degradation in vitro, but their sequence identity was insignificant. Animal polyclonal anti-Gly m 4 and anti-Bet v 1 IgG weakly cross-reacted with Bet v 1 and Gly m 4, respectively. Thus, we supposed that not only conserved epitopes elicited cross-reactivity with Bet v 1, but also variable epitopes were present in the Gly m 4 structure. Our data suggests that consumption of moderately processed soybean-based drinks may lead to the neutralizing of gastric pH as a result of which intact Gly m 4 can reach the human intestine and cause IgE-mediated system allergic reactions.

Mrgprb2 gene plays a role in the anaphylactoid reactions induced by Houttuynia cordata injection.

ETHNOPHARMACOLOGICAL RELEVANCE: Houttuynia cordata Thunb., a plant belonging to the family of Saururaceae, has been used as a traditional Chinese medicine for more than 1500 years. Because of its various pharmacological activities, it was widely used as antipyretic, detoxification, anti-inflammatory drugs. Houttuynia cordata (HC) injection was prepared using contemporary methods to extract effective components from H. cordata Thunb. However, the adverse event reports of HC injection are accumulating remarkably with the HC injection clinical applications increased. Previous studies demonstrated that the major side effects of HC injection were anaphylactoid reactions. Our work might shed the light on the role of Mas-related G-protein coupled receptor-X2 (MRGPRX2) in modulating drug-induced anaphylactoid reactions. AIM OF THE STUDY: We aimed to investigate the role of the mouse Mas-related G-protein coupled receptor B2 (Mrgprb2) (the orthologous gene of human MRGPRX2) in anaphylactoid reactions induced by HC injection. MATERIALS AND METHODS: Mrgprb2 related anaphylactoid reactions induced by HC injection were investigated by histamine/ß-hexosaminidase releasing, mast cell degranulation, and hind paw swelling assays by using a Mrgprb2 knockout mouse model. Furthermore, the transcriptomic profiles of the anaphylactoid reaction induced by HC injection was analyzed by RNA sequencing. RESULTS: Mice without Mrgprb2 exhibited significantly decreasing in mast cell degranulation, serum histamine release, and hind paw swelling degrees. The RNA sequencing results indicated that Mrgprb2 could play a pivotal role in HC injection induced anaphylactoid reaction mediated by mTOR/AMPK pathway. Intriguingly, our results showed that Mrgprb2 might involve in Compound 48/80 induced anaphylactoid reactions mediated by Reelin/E-cadherin axis, which suggested different roles of Mrgprb2 in anaphylactoid reactions induced by HC injection and C48/80. CONCLUSION: Our studies reported effects and underlying mechanisms of Mrgprb2 in the anaphylactoid reaction induced by HC injection.

Anaphylaxis Induced by Intravenous Tacrolimus Administration During Kidney Transplant Surgery: A Case Report.

A 35-year-old male patient with end-stage renal disease due to vesicoureteral reflux preemptively received a renal graft from his father. The patient had a history of allergy to contrast-enhancing media. He received oral tacrolimus (TAC) and mycophenolate mofetil without any problems for 2 days before kidney transplantation. During the induction period of the surgery, his systolic blood pressure (sBP) decreased to 60 mmHg approximately 1 hour after initiating intravenous tacrolimus (TAC-IV) and intravenous piperacillin (PIPC), and the anesthesiologist suspected drug-induced anaphylaxis and stopped administration of the medications. Because TAC had been administered preoperatively without any adverse events, PIPC was suspected as the causative agent of the anaphylaxis. After the patient's hemodynamics returned to baseline, TAC-IV was restarted. However, his sBP rapidly decreased to 40 mmHg and the patient developed wheezing. He was diagnosed with drug-induced anaphylaxis due to castor oil derivatives in the TAC-IV formulation. The patient's sBP was restored with the administration of some vasopressors, and kidney transplantation was then performed without difficulty. Two days after kidney transplantation, oral TAC was administered without anaphylaxis. Clinicians should consider that not only the drug itself but also its additives or metabolites could induce anaphylaxis.

Anaphylaxis following enteral exposure to Chlorella vulgaris.

We present a case of a 75-year-old man who was admitted to an Australian tertiary emergency department with severe hypotension, wheeze, widespread urticarial rash and diarrhoea. On arrival to the emergency department following initial resuscitation by ambulance staff, he was admitted to the intensive care unit with a presumptive diagnosis of gastroenteritis. This diagnosis was later revised following the availability of tryptase levels and clarification of his presenting circumstances, which established a clear temporal relationship between his anaphylactoid symptoms and the oral ingestion of Chlorella vulgaris supplements. While there are a few case studies describing allergic/anaphylactic reactions to several other species of Chlorella, this appears to be the first reported case of anaphylaxis to C. vulgaris.

Occupational buckwheat allergy as a cause of allergic rhinitis, asthma, contact urticaria and anaphylaxis-An emerging problem in food-handling occupations?

Buckwheat is a known, though uncommon, allergen in occupational settings. It has recently gained popularity as healthy food and as an ingredient in gluten-free diets. We describe a series of six patient cases with occupational immediate allergy to buckwheat. Three cooks, two bakers, and a worker in a grocery store were occupationally exposed to buckwheat flour and developed immediate allergy to buckwheat, which was confirmed by skin prick testing and measurement of specific immunoglobulin E antibodies. Four of the patients were diagnosed with occupational asthma, four with occupational rhinitis, and two with occupational contact urticaria caused by buckwheat. Three of the six patients suffered anaphylaxis as consequence of their occupational buckwheat allergy after ingestion of food that contained buckwheat. The high rate of life-threatening reactions, together with a short exposure time to buckwheat before sensitization occurred in these cases, highlights the importance of a detailed occupational history and a high index of suspicion for occupational food allergens.

Anaphylaxis and alternative medicine: an unexpected association.

PURPOSE OF REVIEW: The present review aims to evaluate the use of complementary medicine among patients with allergic disorders, highlighting the risk of adverse reactions, which are often not considered and referred by patients to specialists. RECENT FINDINGS: Complementary medicine is often used in clinical practice and preferred by patients as it is considered a natural therapy compared to traditional medicine. This choice is because of various cultural and socioeconomics aspects. SUMMARY: The use of complementary medicine and its adverse reactions, often as severe as anaphylaxis, is frequently reported in atopic patients, in which a cross reactivity between the natural herbs used and the pollen to which they are sensitized is possible.Therefore, a personalized approach in atopic patients before the use of natural products is crucial to prevent any adverse reactions.

Effects of Mechanical Drying on the Removal of Pollen Allergens.

PURPOSE: Pollen may spread indoors through clothes contaminated during outdoor activities. This study aimed to evaluate the pollen removal efficacy of a mechanical dryer. METHODS: Cotton clothes served as laundry, and fabrics measuring 2 × 5 cm served as test samples. Pollen was spread evenly on the test fabrics. The fabrics were then fixed on the cloth and left for 8 h to imitate real-life conditions. This experiment was conducted under 2 conditions, wet (after washing clothes) and dry (without washing). After drying, we counted pollen on the test fabrics to evaluate the pollen removal rate. We measured the remaining allergens in extracts from the contaminated fabrics after mechanical drying. The concentrations of allergens (Amb a 1, Bet v 1, Crp j 1, and Phl p 1) in each extracted solution were measured using 2-site ELISA. RESULTS: For ragweed, Japanese cedar, birch, and timothy grass, the mean pollen removal ratios for the dry samples were 99.88 ± 0.09%, 99.96 ± 0.03%, 99.89 ± 0.02%, and 99.82 ± 0.11%, respectively, and those for the wet samples were 98.83 ± 0.87%, 97.91 ± 1.81%, 97.29 ± 1.19%, and 96.3 ± 0.92%, respectively. Further, for the pollen allergens Amb a 1 [ragweed], Crp j 1 [Japanese cedar], Bet v 1 [birch], and Phl p 1 [timothy grass], the mean pollen allergen removal ratios for the dry samples were 99.81 ± 0.06%, 99.94 ± 0.23%, 99.90 ± 0.11%, and 99.84 ± 0.17%, respectively, and those for the wet samples were 98.11 ± 0.14%, 96.04 ± 1.52%, 97.21 ± 0.83%, and 95.23 ± 0.92%, respectively. There was no statistically significant difference for each species. CONCLUSIONS: Mechanical drying effectively removed pollen and allergens from dry and wet fabrics. We expect that further studies on the removal of other indoor allergens would contribute to improved environmental control for allergy patients.