Clinical significance of plasma PAF acetylhydrolase activity measurements as a biomarker of anaphylaxis: Cross-sectional study.

INTRODUCTION: Platelet-activating factor (PAF) has a direct role as a mediator in the pathogenesis of various disorders with an inflammatory component, including those with allergic aetiology. The peripheral blood concentration of PAF is dynamically regulated by plasma PAF acetylhydrolase (PAF-AH). Previous research suggest that low activity of plasma PAF-AH could be a predictive marker for increased severity of some types of allergic hypersensitivity reactions-especially anaphylaxis. The purpose of the study was to evaluate the association between plasma PAF-AH activity and severity in patients with anaphylactic reactions following a wasp or bee sting. MATERIALS AND METHODS: The study group of 89 patients was divided into two subgroups depending on the increasing severity of the most severe anaphylactic reaction in the past, which was assessed according to the Müller's scale. The first subgroup included participants with a history of hypersensitivity reactions up to grade II. The second subgroup consisted of patients who have experienced at least one grade III or IV reactions in the past. A control group of 20 people was established. Plasma PAF-AH activity was measured using a colorimetric method. RESULTS: It has been observed that plasma activity of platelet-activating factor acetylhydrolase was significantly lower in patients with anaphylaxis history compared to the control group with negative atopic history (on average 21.38 nmol/min/ml for the control group, 9.47 nmol/min/ml for the first subgroup and 10.16 nmol/min/ml for the second subgroup, in both cases p < 0.0001). CONCLUSION: The plasma activity of PAF-AH is a promising parameter that can help to distinguish a group of patients not threatened with development of anaphylaxis and not requiring laborious or expensive prophylactic procedures.

What's eating you? vespids revisited.

The Hymenoptera order of insects includes Apidae (bees), Vespidae (wasps, yellow jackets, hornets), and Formicidae (fire ants). All 3 of these families of insects inject venom into their prey or as a defense mechanism via ovipositors in their abdomen. Three types of reactions can be seen after a vespid sting: uncomplicated local reactions, large local reactions, and systemic reactions (SRs). Although many vespid stings can be managed symptomatically, it is imperative for patients and providers to be aware of the possible severe reactions that can take place.

A Preliminary Report of the Relationship Between Gene Polymorphism of IL-8 and Its Receptors and Systemic Inflammatory Response Syndrome Caused by Wasp Stings.

The plasma levels of interleukin-8 (IL-8) and its receptors (CXCR1 and CXCR2) play a significant role in the development of systemic inflammatory response syndrome (SIRS), but it is not clear how these proteins are involved in wasp sting patients developing SIRS. To study potential genetic factors predisposing to the risk of SIRS caused by wasp sting injury, we determined the plasma levels of IL-8 and its receptors among SIRS patients with wasp sting injury and investigated the association of single-nucleotide polymorphisms of these genes with SIRS. A total of 225 patients were divided into the SIRS group (n = 62) and non-SIRS group (control, n = 163), and we associated polymorphisms in IL-8 [rs4073 (-251T>A), rs2227532 (-845C>T), rs2227307 (+396G>T), rs2227306 (+781T>C), CXCR1 rs2234671 (+860C>G), CXCR2 [rs2230054 (+811T>C), rs57929613 (+1235C>T), and rs60626131 (+1440A>G)] with SIRS with a linear additive model. In terms of protein expression, the IL-8, CXCR1, and CXCR2 plasma levels were significantly higher in the SIRS group than in the control group (p < 0.001). Significantly higher frequencies were observed for the IL-8 - 251T allele (AT+TT), CXCR2 + 811T allele (CT+TT), and +1235C allele (TC+CC) in the SIRS group, when compared with the control group, with odds ratio (OR) = 3.971 (95% confidence interval [CI], 1.618-9.734), p = 0.003; OR = 4.223 (95% CI, 1.863-9.571), p = 0.001; and OR = 4.012 (95% CI, 1.773-9.079), p = 0.001; respectively. In addition, SIRS is more likely to occur in males, patients with number of wasp stings ≥10 stings, and stings in the limbs. The current study suggests that the IL-8 - 251T allele (AT+TT) and IL-8 receptor CXCR2 + 811C allele (CT+TT) and +1235T allele (TC+CC) could be risk factors among SIRS patients with wasp sting injury.

Ant Bites Conjunctival Tissue: The ABCs of Removing an Ocular Ant Foreign Body.

BACKGROUND: A variety of insect-related ocular injuries have been reported in the literature. However, no reports have been published documenting injuries resulting from exposure of the ocular surface to ants. This is surprising, given the relatively ubiquitous presence of ants. This is the first known case report to describe various techniques utilized in the removal of ants from the ocular surface. CASE REPORT: This case report details the presentation of a distressed 24-year-old woman who presented to the Emergency Department with an ocular foreign body associated with pain and increased lacrimation. She was identified to have an ant adherent to her conjunctiva. Various techniques of removal were performed, with the ant finally removed without any trauma to underlying tissues. CONCLUSION: This is the first case report to detail various techniques utilized in the removal of ants from the ocular surface, and discusses salient features that treating physicians should be aware of in managing patients presenting with ant bites.

Physiological and immunological responses to Culicoides sonorensis blood-feeding: a murine model.

BACKGROUND: Hematophagous Culicoides spp. biting midges are of great agricultural importance as livestock, equine, and wildlife pests and as vectors of the orbiviruses bluetongue, epizootic hemorrhagic disease and African horse sickness. To obtain a blood meal, midges deposit saliva containing allergens, proteases, and anti-hemostatic factors, into the dermis to facilitate feeding. Infected midges deposit virus along with the myriad of salivary proteins during feeding. The extreme efficiency with which midges are able to transmit orbiviruses is not clearly understood, as much is still unknown about the physiological trauma of the bite and immune responses to saliva deposited during feeding. Of particular interest are the first few hours and days after the bite; a critical time period for any midge-transmitted virus to quickly establish a localized infection and disseminate, while avoiding the hosts' immune responses. RESULTS: A mouse-midge feeding model using colonized Culicoides sonorensis midges was used to characterize innate mammalian immune responses to blood-feeding. Histological analysis of skin, and cellular and cytokine profiles of draining lymph nodes show Culicoides midge feeding elicited a potent pro-inflammatory Th-mediated cellular response with significant mast cell activation, subcutaneous hematomas, hypodermal edema and dermal capillary vasodilation, and rapid infiltration of leukocytes to the bite sites. Mast cell degranulation, triggered by bite trauma and specifically by midge saliva, was key to physiological and immunological responses and the ability of midges to feed to repletion. CONCLUSIONS: Midge feeding causes physiological and immunological responses that would be highly favorable for rapid infection and systemic dissemination orbiviruses if delivered during blood-feeding. Recruitment of leukocytic cells to bitten skin brings susceptible cell populations in proximity of deposited virus within hours of feeding. Infected cells would drain to lymph nodes, which become hyperplastic in response to saliva, and result in robust viral replication in expanding cell populations and dissemination via the lymph system. Additionally, saliva-induced vasodilation and direct breaches in dermal capillaries by biting mouthparts exposes susceptible vascular endothelial cells, thereby providing immediate sites of virus replication and a dissemination route via the circulatory system. This research provides insights into the efficiency of Culicoides midges as orbivirus vectors.

Soft tissue calcifications secondary to Hymenoptera stings: a potential prognostic CT imaging sign in pediatric patients.

CONTEXT: Soft tissue calcifications (STCs) were incidentally found in some of the Hymenoptera-stung (HS) children when they underwent computed tomography (CT) scans for evaluating complications of vital organs. Afterwards, a predilection of STCs to the children with severe complications was clinically noticed. A hypothesis was then developed that STCs secondary to HS may correlate with poor outcomes. OBJECTIVE: This study aims to firstly characterize the CT findings of STCs in HS children and to confirm our hypothesis that the occurrence of STCs may act as an indicator of poor outcomes in HS children. MATERIALS AND METHODS: Children who received CT scanning after Hymenoptera sting from January 2011 to October 2016 in our hospital were analyzed retrospectively. Shape, location, and distribution of the STCs were described according to the CT findings. Then the enrolled cases were classified into Soft Tissue Calcification Group (STCG) and non-Soft tissue Calcification Group (non-STCG) to conduct prognostic comparisons of Sequential Organ Failure Assessment (SOFA) scores, incidence of main complications (acute liver failure (ALF), acute kidney injury stage III (AKI-III) and multiple organ failure (MOF)), length of hospital days, and in-hospital death, respectively. Pearson correlation was also utilized between the cumulative volume of STCs and the SOFA score. RESULTS: Sixteen cases were enrolled, and STCs' incidence was 56.25% (9/16). Two STCG cases had diffuse nodular calcifications in their swollen subcutaneous tissue, and another seven had symmetrically stripy or patchy calcifications within or along local muscles. The SOFA scores during the first 3 days were all higher in STCG, and rose to the greatest difference at the third day (9.78 ± 2.17 vs. 2.29 ± 2.06, t = 7.009, p < .001); the incidence of ALF, AKI-III and MOF were significantly higher in STCG (66.67% vs. 0, p = .011), (77.78% vs. 0, p = .003) and (77.78% vs. 14.29%, p = .041); and children in STCG were treated with longer hospital durations (26.33 ± 8.41 days vs. 12.29 ± 7.36 days, t = 3.493, p = .004). One child in STCG died of cardiopulmonary failure, and no deaths occurred in non-STCG. No significant correlations presented between STCs cumulative volumes and SOFA score (rDay1 = 0.096, p = .806; rDay2 = 0.067, p = .863; rDay3 = 0.024, p = .950). CONCLUSION: Soft tissue calcifications detected on CT imaging following multiple Hymenoptera stings in pediatric patients may be a potential prognostic indicator of more severe complications and poorer outcomes.

Cutaneous hemophagocytosis: Clinicopathologic features of 21 cases.

BACKGROUND: Hemophagocytosis is well known in cytotoxic cutaneous T-cell lymphomas (CTCLs), in which it may represent a sign of hemophagocytic lymphohistiocytosis syndrome (HLHS), and is also typical of cutaneous Rosai-Dorfman disease (cRDD) (without prognostic relevance). Only rarely, has cutaneous hemophagocytosis (CH) been described in other skin conditions. OBJECTIVE: To characterize the clinicopathologic features of CH in skin biopsy specimens from patients with conditions other than CTCL or cRDD. METHODS: Case series analyzing clinicopathologic features and follow-up data on patients presenting with histopathologic signs of CH. RESULTS: Biopsy specimens from 21 patients were included. None of the patients had HLHS. The majority (n = 11) presented with leukocytoclastic vasculitis. Other associated diseases were lupus erythematous (n = 2), arthropod bite reaction (n = 2), erysipelas (n = 1), acne conglobata (n = 1), and Sweet syndrome (n = 1). Three patients had a nonspecific rash concomitant with Chlamydia pneumonia, middle ear infection, and pharyngitis, respectively. LIMITATIONS: This was a single-center, retrospective study. CONCLUSION: Isolated CH in conditions other than CTCL and cRDD is a histopathologic finding related mostly to leukocytoclastic vasculitis. Extensive investigations should be performed only if patients have other signs or symptoms of HLHS.

Which immunotherapy product is better for patients allergic to Polistes venom? A laboratory and clinical study.

BACKGROUND: Venom immunotherapy (VIT) is highly effective in preventing allergic reactions to insect stings, but the appropriate venom must be used to achieve clinical protection. In patients with multiple positive results to venoms, molecular allergy diagnostics or CAP-inhibition may identify the causative venom. Concerning allergy to venom from Polistes spp. it has been proposed that only the European species P. dominulus should be used for VIT. However, this recommendation is not present in any international guideline. Using both laboratory and clinical data, we aimed to evaluate the reliability of this proposal. METHODS: We performed an in vitro study using CAP-inhibition to determine sensitization of 19 patients allergic to Polistes venom. The clinical study included 191 patients with positive tests to Polistes treated with VIT, 102 were treated with P. dominulus and 89 were treated with a mix of American Polistes (mAP). RESULTS: The difference in % of inhibition was significant concerning inhibition of P. dominulus sIgE by P. dominulus venom (79.8%) compared with inhibition by mAP venom (64.2%) and not significant concerning the inhibition of mAP sIgE by P. dominulus venom (80.1%) and by mAP venom (73.6%). Instead, the clinical protection from stings was not statistically different between the two kinds of venom. CONCLUSION: The data from CAP inhibition would suggest that the choice of either P. dominulus venom or mAP venom for VIT is appropriate in patients with CAP inhibition higher than 70%, but the clinical data show the same odds of protection from stings using for VIT P. dominulus or mAP venom.

Human scFv antibodies (Afribumabs) against Africanized bee venom: Advances in melittin recognition.

Africanized Apis mellifera bees, also known as killer bees, have an exceptional defensive instinct, characterized by mass attacks that may cause envenomation or death. From the years 2000-2013, 77,066 bee accidents occurred in Brazil. Bee venom comprises several substances, including melittin and phospholipase A2 (PLA2). Due to the lack of antivenom for bee envenomation, this study aimed to produce human monoclonal antibody fragments (single chain fragment variable; scFv), by using phage display technology. These fragments targeted melittin and PLA2, the two major components of bee venom, to minimize their toxic effects in cases of mass envenomation. Two phage antibody selections were performed using purified melittin. As the commercial melittin is contaminated with PLA2, phages specific to PLA2 were also obtained during one of the selections. Specific clones for melittin and PLA2 were selected for the production of soluble scFvs, named here Afribumabs: prefix: afrib- (from Africanized bee); stem/suffix: -umab (fully human antibody). Afribumabs 1 and 2 were tested in in vitro and in vivo assays to assess their ability to inhibit the toxic actions of purified melittin, PLA2, and crude bee venom. Afribumabs reduced hemolysis caused by purified melittin and PLA2 and by crude venom in vitro and reduced edema formation in the paws of mice and prolonged the survival of venom-injected animals in vivo. These results demonstrate that Afribumabs may contribute to the production of the first non-heterologous antivenom treatment against bee envenomation. Such a treatment may overcome some of the difficulties associated with conventional immunotherapy techniques.

Anaphylaxis caused by stings from the Solenopsis invicta, lava-pés ant or red imported fire ant.

Ants are social insects with species of medical interest, such as the fire ants (Solenopsis sp.). The sting causes inflammation, vesicles and sterile pustules, which may cause allergic phenomena and even anaphylactic shock. We describe a patient who suffered a large number of stings and an episode of syncope with fall in blood pressure and complete regression of symptoms after resuscitation and medication for anaphylaxis. Considering the clinical manifestations and images of wheals and blisters on the patient's feet at the time of syncope, this report should serve as a warning for the diagnosis and treatment of this condition and even for counseling and prevention regarding patients exposed to this risk.

Anaphylaxis caused by stings from the Solenopsis invicta, lava-pés ant or red imported fi re ant

Ants are social insects with species of medical interest, such as the fi re ants (Solenopsis sp.). The sting causes inflammation, vesicles and sterile pustules, which may cause allergic phenomena and even anaphylactic shock. We describe a patient who suffered a large number of stings and an episode of syncope with fall in blood pressure and complete regression of symptoms after resuscitation and medication for anaphylaxis. Considering the clinical manifestations and images of wheals and blisters on the patient’s feet at the time of syncope, this report should serve as a warning for the diagnosis and treatment of this condition and even for counseling and prevention regarding patients exposed to this risk.

Bee and wasp stings in Deniyaya; a series of 322 cases.

OBJECTIVES: To describe wasp and bee species that sting humans, analyse risk factors and clinical features. METHODS: A prospective observational study was conducted on patients presenting to Base Hospital Deniyaya with suspected bee and wasp stings from 2011 to 2013. Data were gathered using a questionnaire and specimens of offending insects collected for identification. When the insect specimen was unavailable, identification was made by the victim selecting (without prompting) from several dead specimens presented by the first author. RESULTS: There were 322 patients (mean age: 42.5 years, SD: 15.1, 173 [53.7%] males). Insects were brought by 55 (17%) and 267 (83%) were identified using specimens. All occurred during day-time, 142 (44.1%) during August and September, and 200 victims (62%) were tea plantation workers. Majority (78.9%) reported a localized painful self-limiting swelling without systemic features and 15 (4.6%) developed anaphylactic shock. None died. Five specimens were available from those in anaphylactic shock (four Apis dorsata, one Ropalidia marginata). Vespa tropica stinging caused a characteristic skin lesion. Of the 55 specimens, 46 (83.6%) were Apis dorsata (Giant honey-bee, ''Bambara''), 8 (14.5%) Vespa tropica (Greater banded hornet, ''Debara'') and one Ropalidia marginata (Paper wasp, ''Kaladuruwa''). CONCLUSIONS: Only three hymenoptera species stings were reported. Risk factors included day-time outdoor activities, occupation (tea plantation workers) and period of year. The latter may be due to pollen season when the insects are found in abundance. Only 4.6% of the patients developed anaphylactic shock. Vespa tropica stings led to a unique skin lesion.

Kounis syndrome: a stinging case of ST-elevation myocardial infarction.

Kounis syndrome is not a rare but an infrequently diagnosed non-thrombogenic cause of angina or myocardial infarction triggered by the release of inflammatory mediators following an allergic or anaphylactic reaction. This so-called "allergic angina" is seen in the setting of anaphylactic reactions and is believed to be due to mast cell release causing coronary vasospasm. The treatment of such cases is often with epinephrine, which has also been described in the literature as another rare cause of coronary vasospasm. We present a case of Kounis syndrome seen in a 46 year-old male who suffered two bee stings while landscaping in his yard. He developed an anaphylactic reaction and was promptly treated with IM epinephrine injection by paramedics at arrival and developed marked ST elevations on EKG in the inferior leads with reciprocal ST depressions in the anterior leads. His troponin peaked at 13 ng/mL and tryptase level was 15 ng/mL (normal <10 ng/mL). Coronary catheterisation showed non-diseased coronary arteries and a normal ejection fraction without evidence of vasospasm. He was afterwards treated with an epinephrine drip for distributive shock. Interestingly this syndrome was not provoked when re-challenged with this therapy, suggestive of an allergic reaction rather than epinephrine as the aetiology of his presumed vasospasm. This patient's ST segment elevation and troponin elevation was due to Kounis syndrome. Awareness that anaphylactic reactions can lead to Kounis syndrome can lead to prompt appropriate treatment for this life threatening condition.