Single-Arm, Multicenter Phase I/II Clinical Trial for the Treatment of Envenomings by Massive Africanized Honey Bee Stings Using the Unique Apilic Antivenom.

We evaluated the safety, optimal dose, and preliminary effectiveness of a new-approach Africanized honeybee (Apis mellifera) Antivenom (AAV) in a phase I/II, multicenter, non-randomized, single-arm clinical trial involving 20 participants with multiple stings. Participants received 2 to 10 vials of AAV depending on the number of stings they suffered, or a predefined adjuvant, symptomatic, and complementary treatment. The primary safety endpoint was the occurrence of early adverse reactions within the first 24 h of treatment. Preliminary efficacy based on clinical evolution, including laboratory findings, was assessed at baseline and at various time points over the four following weeks. ELISA assays and mass spectrometry were used to estimate venom pharmacokinetics before, during, and after treatment. Twenty adult participants, i.e., 13 (65%) men and 7 (35%) women, with a median age of 44 years and a mean body surface area of 1.92 m2 (median = 1.93 m2) were recruited. The number of stings ranged from 7 to > 2,000, with a median of 52.5. Symptoms of envenoming were classified as mild, moderate, or severe in 80% (16), 15% (3), and 5% (1) of patients, respectively; patients with mild, moderate, or severe envenoming received 2, 6, and 10 vials of AAV as per the protocol. None of the patients had late reactions (serum sickness) within 30 d of treatment. There was no discontinuation of the protocol due to adverse events, and there were no serious adverse events. One patient had a moderate adverse event, transient itchy skin, and erythroderma. All participants completed the intravenous antivenom infusion within 2 h, and there was no loss to follow-up after discharge. ELISA assays showed venom (melittin and PLA2) concentrations varying between 0.25 and 1.479 ng/mL prior to treatment. Venom levels decreased in all patients during the hospitalization period. Surprisingly, in nine cases (45%), despite clinical recovery and the absence of symptoms, venom levels increased again during outpatient care 10 d after discharge. Mass spectrometry showed melittin in eight participants, 30 d after treatment. Considering the promising safety results for this investigational product in the treatment of massive Africanized honeybee attack, and its efficacy, reflected in the clinical improvements and corresponding immediate decrease in blood venom levels, the AAV has shown to be safe for human use. Clinical Trial Registration: UTN: U1111-1160-7011, identifier [RBR-3fthf8].

Cross-Reactive Carbohydrate Determinant in Apis mellifera, Solenopsis invicta and Polybia paulista Venoms: Identification of Allergic Sensitization and Cross-Reactivity.

Allergic reactions to Hymenoptera venom, which could lead to systemic and even fatal symptoms, is characterized by hypersensitivity reactions mediated by specific IgE (sIgE) driven to venom allergens. Patients multisensitized to sIgE usually recognize more than one allergen in different Hymenoptera species. However, the presence of sIgE directed against Cross-Reactive Carbohydrate Determinant (CCD), which occurs in some allergens from Hymenoptera venom, hampers the identification of the culprit insects. CCD is also present in plants, pollen, fruits, but not in mammals. Bromelain (Brl) extracted from pineapples is a glycoprotein commonly used for reference to sIgE-CCD detection and analysis. In sera of fifty-one Hymenoptera allergic patients with specific IgE ≥ 1.0 KU/L, we assessed by immunoblotting the reactivity of sIgE to the major allergens of Apis mellifera, Polybia paulista and Solenopsis invicta venoms. We also distinguished, using sera adsorption procedures, the cases of CCD cross-reaction using Brl as a marker and inhibitor of CCD epitopes. The presence of reactivity for bromelain (24-28 kDa) was obtained in 43% of the patients, in which 64% presented reactivity for more than one Hymenoptera venom in radioallergosorbent (RAST) tests, and 90% showed reactivity in immunoblot analysis to the major allergens of Apis mellifera, Polybia paulista and Solenopsis invicta venoms. Sera adsorption procedures with Brl lead to a significant reduction in patients' sera reactivity to the Hymenoptera allergens. Immunoblotting assay using pre- and post-Brl adsorption sera from wasp-allergic patients blotted with non-glycosylated recombinant antigens (rPoly p1, rPoly p5) from Polybia paulista wasp venom showed no change in reactivity pattern of sIgE that recognize allergen peptide epitopes. Our results, using Brl as a marker and CCD inhibitor to test sIgE reactivity, suggest that it could complement diagnostic methods and help to differentiate specific reactivity to allergens' peptide epitopes from cross-reactivity caused by CCD, which is extremely useful in clinical practice.

Pediatric envenomations: don't get bitten by an unclear plan of care.

Children are frequently victims of terrestrial animal and insect bites and stings. While the majority of these bites or stings are nondangerous, pediatric patients occasionally encounter a venomous animal. In such cases, children may present to the emergency department for evaluation and management. This review presents the basic epidemiology of bites and stings of spiders, bees and wasps, fire ants, scorpions, and snakes, but it primarily focuses on the underlying pathophysiology and clinical presentation of the envenomated patient. While the pathophysiology and much of the presentation and treatment are the same for both children and adults, there are occasionally subtle differences, which will be highlighted. The management and disposition of pediatric patients for each type of bite or sting will also be discussed.

Arthropod bites.

The phylum Arthropoda includes arachnids and insects. Although their bites typically cause only local reactions, some species are venomous or transmit disease. The two medically important spiders in the United States are widow spiders (Latrodectus), the bite of which causes intense muscle spasms, and the brown recluse (Loxosceles), which may cause skin necrosis. Widow bites usually respond to narcotics, benzodiazepines, or, when necessary, antivenom. Most recluse bites resolve uneventfully without aggressive therapy and require only wound care and minor debridement. Tick bites can transmit diseases only after prolonged attachment to the host. Treatment of clothing with permethrin and proper tick removal greatly reduce the risk of infection. Ticks of medical importance in the United States include the black-legged tick, the Lone Star tick, and the American dog tick. The prophylactic use of a single dose of doxycycline for Lyme disease may be justified in high-risk areas of the country when an attached, engorged black-legged tick is removed. Bites from fleas, bedbugs, biting flies, and mosquitoes present as nonspecific pruritic pink papules, but the history and location of the bite can assist with diagnosis. Flea bites are usually on ankles, whereas mosquito bites are on exposed skin, and chigger bites tend to be along the sock and belt lines. Antihistamines are usually the only treatment required for insect bites; however, severe mosquito reactions (skeeter syndrome) may require prednisone. Applying insect repellent containing diethyltoluamide (DEET) 10% to 35% or picaridin 20% is the best method for preventing bites.

Insect-bite-like reaction in patients with chronic lymphocytic leukemia: a study from the Israeli Chronic Lymphocytic Leukemia Study Group.

An insect-bite-like reaction is known to occur in patients with chronic lymphocytic leukemia (CLL). Most of the literature, however, consists of isolated case reports or small case series. The aim of this retrospective study was to review the national experience with insect-bite-like reaction in a large group of patients with CLL. The study cohort of patients with these skin reactions consisted of 48 patients (25 males, 23 females) of mean age 64.8 yr (range 33-89) at skin eruption. Data on clinical, histologic, immunophenotypic, and cytogenetic characteristics, treatment, and outcome were collected from the medical files. Mean time between diagnosis of CLL and appearance of the skin lesions was 3.1 yr (range -4 to 14 yr). The eruption was not related to disease activity or the course of the hematological disease. The eruption preceded the diagnosis of CLL in 10 patients (by 0-4 yr); and followed the diagnosis in 36; in 11 patients, it occurred during therapy for CLL and in nine after therapy. Mean duration of the skin findings was 21.5 months (range 0.3-132). The eruption usually presented in summer, although it occurred also at other times of the year, and predominantly affected the upper and lower limbs, although it also appeared on unexposed areas. Treatment included local ointments, antihistaminics, oral steroids, antibiotics, phototherapy, and dapsone with varying responses. Insect-bite-like reactions is a relatively common and disturbing skin reaction in CLL patients, it may be related to the immune dysregulation accompanying CLL and further exacerbated by external factors, including actual insect bites, chemoimmunotherapy, and pyogenic infection.

Novel use of 308-nm excimer laser to treat a primary cutaneous CD30+ lymphoproliferative nodule.

CD30+ cutaneous lymphoproliferative disorders, the second most common cutaneous T cell lymphoma after mycosis fungoides, represent a spectrum of conditions ranging from lymphomatoid papulosis to borderline CD30+ lesions to anaplastic large-cell lymphoma. We report the case of a solitary cutaneous CD30+ lymphoproliferative nodule that was successfully treated with a 308-nm excimer laser. Our findings suggest that the 308-nm excimer laser may be a safe, effective, and well-tolerated therapy for primary localized CD30+ cutaneous lymphoproliferative lesions.

Late Horner's syndrome following the bite of a black widow spider.

In this paper, we report on the case of a 23-year-old man who presented with a ptosis of the right upper lid and a miosis 1 month after being bitten in his right hand by Latrodectus revivenis. A positive cocaine test confirmed a diagnosis of Homer's syndrome.

Diagnósticos hechos a 1384 pacientes que consultaron por probable mordedura de arañas o picaduras de insectos / Diagnosis done to 1384 patients which had consulted for a probable spider bite or insect sting

Accumulate experience, from 1955 to 1995, in an outpatient univesity parasitology clinic in Santiago, which 1384 patients referred from diverse public and private medical institutions because of a probable spider bite or insect stings, is presented. It is noteworthy that only 618 (44,7 percent) of consultations corresponded to clinical conditions originated by arthropods, whereas from the remaining 766, 612 (44,2 percent) were due to a bacterial, viral or parasitic etiology and 154 (11,1 percent) were caused by physical or chemical agents. Frecuency of diagnosis was: loxoscelism 16,6 percent, spider bites (excluded loxosceles laeta) 1,3 percent, scorpion stings 0,9 percent, tick stings 2,2 percent insect bites 23,7 percent, impetigo 6,6 percent, folliculitis 11,3 percent, boil 22,7 percent, erysipelas 0,1 percent, pustula maligna 0,3 percent, herpes simplex 2,5 percent, palpebral herpes zoster 0,3 percent, acute Chagas's disease 0,4 percent, angioneurotic edema 0,1 percent, ecchymosis 3,0 percent, contact dermitis 7,8 percent and chemical dermitis 0,2 percent. These frequencies do not indicate the real occurrence of the diagnosed nosologies, but what happened in a specialized outpatient clinic dealing cheafly with parasitic diseases and arthropod envenomations. Description of relevant clinical features and epidemiological considerations of pathology observed conjointly with differential diagnosis are presented

Total serum IgE concentrations in adolescents and adults using the phadebas IgE PRIST technique.

Total serum IgE measured with the Phadebas PRIST technique was titrated in 117 normal non-allergic subjects, 237 allergic adolescents or adults and 89 non-allergic patients who suffered from asthma, rhinitis, or conjunctivitis. All subjects were of Caucasian origin. In normal subjects, mean total serum IgE was 38 +/- 43 kU/l. This value is exactly the same as that found in a study of Caucasian New Zealanders and very similar to the values found in most U.S. studies. This suggests that the mean total serum IgE concentration is remarkably constant in normal non-allergic Caucasians. The upper limit of the normal range is considered to be 150 kU/l. 38% of allergic patients have total IgE concentrations within the normal range. Some pollen or hymenoptera venom-sensitive patients have a total serum IgE concentration below 20 kU/l. The non-allergic patients had a mean IgE concentration of 94 +/- 93 kU/l, and 25% of them had a total serum IgE above the normal range. Asthmatic patients had higher mean IgE levels than those who were suffering from either rhinitis or conjunctivitis.