Honeybee Sting Research Articles

Eosinophilic Cellulitis After Honeybee Sting

Stings by honeybees are not uncommon and most cases cause pain but no significant medical problems. Some patients, however, have lethal complications such as acute anaphylactic shock. Cellulitis caused by honeybee sting is very rare and can be a late complication in some patients. We report a 45-year-old female patient who was stung by a honeybee, and whose right forearm showed progressive swelling with bullous formation after the sting. She was sent to our emergency department with the diagnosis of right hand cellulitis. After treatment with antibiotics for 5 days, the lesions showed no response. Then, systemic steroid was used and the lesion gradually resolved. Diagnosis of Wells syndrome was made according to clinical appearance, course and characteristic histopathological findings.

Reducing Honey Bee Defensive Responses and Social Wasp Colonization With Methyl Anthranilate

Human victims of a massive number of stings have been steadily increasing since the invasion of Africanized honey bees (Apis mellifera) to the United States in 1990. Multiple honey bee stings may result in venom toxicity, leading to renal failure and even death. Here we tested the efficacy of methyl anthranilate as a honey bee repellent during a massive defensive response by Africanized honey bees. An aerosolized solution of 10% methyl anthranilate reduced the number of defensive bee hits to a retreating victim by 95% compared with a water control. One hundred fifty milliliters of the 10% methyl anthranilate solution sprayed onto stationary foam balls covered with black suede leather located 2 m from provoked Africanized colonies received 80% fewer stings than targets treated with water. Methyl anthranilate (100%) delivered through a UV blocking 3 mil polyethylene pouch was 100% effective in preventing Polistes colonization in wildlife observation huts and from the roof overhang of home patios. Although methyl anthranilate was not 100% effective in preventing honey bee stinging, it seemed to reduce number of stings below the average human LD50, indicative of a promising tool for preventing honey bee venom toxicity and wasp colonization.

Trigeminal neuropathic pain following honeybee sting: a case report

The neurological complications of bee venom poisoning vary from optic neuritis to pontine hematoma. However, to our best knowledge, trigeminal neuropathic pain secondary to bee sting has not been reported previously in the literature. We report the case of a 52-year-old male patient with right-sided trigeminal neuropathic pain that began a month earlier, following a honeybee sting to the right forehead. The patient was successfully treated by CT-guided percutaneous trigeminal tractotomy. The present report demonstrated that a honeybee sting may result in trigeminal neuropathic pain and CT-guided percutaneous trigeminal tractotomy is effective in the treatment of such cases.

Sublingual immunotherapy for large local reactions caused by honeybee sting: A double-blind, placebo-controlled trial

Sublingual immunotherapy (SLIT) proved effective and safe in respiratory allergy, and thus its use in hymenoptera allergy can be hypothesized. We sought to assess, in a proof-of-concept study, whether SLIT might potentially be beneficial in hymenoptera allergy. The sting challenge in large local reactions (LLRs) was used to test this hypothesis. We performed a randomized, double-blind, placebo-controlled study involving patients with LLRs who were monosensitized to honeybee. After the baseline sting challenge, they were randomized to either SLIT or placebo for 6 months. The treatment (Anallergo, Florence, Italy) involved a 6-week build-up period, followed by maintenance with 525 microg of venom monthly. The sting challenge was repeated after 6 months. Thirty patients (18 male patients; mean age, 44.5 years) were enrolled, and 26 completed the study, with 1 dropout in the active group and 3 dropouts in the placebo group. In the active group the median of the peak maximal diameter of the LLRs decreased from 20.5 to 8.5 cm (P = .014), whereas no change was seen in the placebo group (23.0 vs 20.5 cm, P = not significant). The diameter was reduced more than 50% in 57% of patients. One case of generalized urticaria occurred in a placebo-treated patient at sting challenge. No adverse event caused by SLIT was reported. Honeybee SLIT significantly reduced the extent of LLRs, and its safety profile was good. Although LLRs are not an indication for immunotherapy, this proof-of-concept study suggests that SLIT in hymenoptera allergy deserves further investigation. Trials involving systemic reactions and dose-ranging studies are needed.

Cellular in vitro Assays in the Diagnosis of Hymenoptera Venom Allergy

Background: The current diagnostic procedures of anaphylactic reactions to hymenoptera stings include intradermal tests, venom-specific IgE (sIgE) and possibly sting challenge tests. Sometimes, the culprit insect remains unidentified. The usefulness of the cellular assays CAST®-ELISA and Flow-CAST® in the management of hymenoptera venom allergy was investigated. Methods: 134 patients with systemic reactions after a yellow jacket wasp and/or honey bee sting and 44 healthy controls underwent skin tests, as well as determination of sIgE (CAP-FEIA), leukocyte sulfidoleukotriene release (CAST-ELISA) and basophil CD63 expression (Flow-CAST) upon insect venom stimulation. The clinical diagnosis based on the history alone served as reference. Sensitivity, specificity, and positive and negative predictive value of all methods were compared. Concordance and correlations among methods were calculated. Results: Sensitivity and specificity of all in vitro tests were consistently high. The combination of all tests (skin tests, sIgE, combined cellular assays) yielded a positive predictive value of 100% for both venoms, if all 3 were positive, and a negative predictive value of 100%, if at least 1 test was positive. Relative specificities were considerably higher for the cellular assays (honey bee: CAST 91.1%, Flow-CAST 85.7%; yellow jacket wasp: CAST 98.4%, Flow-CAST 92.1%) and allow the detection of the culprit insect in patients with reactivity to both insects. The concordance between methods was good. There is no correlation between severity of clinical reaction and cellular assays. Conclusion: CAST-ELISA and Flow-CAST are valuable additional diagnostic tools for establishing the true culprit insect in patients with unclear clinical history or sensitization to both insects.

Differential Activation of p38 and Extracellular Signal-Regulated Kinase in Spinal Cord in a Model of Bee Venom-Induced Inflammation and Hyperalgesia

BackgroundHoneybee's sting on human skin can induce ongoing pain, hyperalgesia and inflammation. Injection of bee venom (BV) into the intraplantar surface of the rat hindpaw induces an early onset of spontaneous pain followed by a lasting thermal and mechanical hypersensitivity in the affected paw. The underlying mechanisms of BV-induced thermal and mechanical hypersensitivity are, however, poorly understood. In the present study, we investigated the role of mitogen-activated protein kinase (MAPK) in the generation of BV-induced pain hypersensitivity.ResultsWe found that BV injection resulted in a quick activation of p38, predominantly in the L4/L5 spinal dorsal horn ipsilateral to the inflammation from 1 hr to 7 d post-injection. Phosphorylated p38 (p-p38) was expressed in both neurons and microglia, but not in astrocytes. Intrathecal administration of the p38 inhibitor, SB203580, prevented BV-induced thermal hypersensitivity from 1 hr to 3 d, but had no effect on mechanical hypersensitivity. Activated ERK1/2 was observed exclusively in neurons in the L4/L5 dorsal horn from 2 min to 1 d, peaking at 2 min after BV injection. Intrathecal administration of the MEK inhibitor, U0126, prevented both mechanical and thermal hypersensitivity from 1 hr to 2 d. p-ERK1/2 and p-p38 were expressed in neurons in distinct regions of the L4/L5 dorsal horn; p-ERK1/2 was mainly in lamina I, while p-p38 was mainly in lamina II of the dorsal horn.ConclusionThe results indicate that differential activation of p38 and ERK1/2 in the dorsal horn may contribute to the generation and development of BV-induced pain hypersensitivity by different mechanisms.

Necrotizing fasciitis after a honey bee sting

Necrotizing soft-tissue infections such as necrotizing fasciitis continue to have a high morbidity and mortality. More and more, these difficult cases are being referred to burn centers for specialized wound and critical care treatment. The case of a necrotizing soft-tissue infection after a honeybee sting is reported. To the best of our knowledge, it is the first documented case of necrotizing fasciitis caused by invasive group A Streptococcus from a bee sting. A 56-year-old man was stung by a bee in the left upper gluteal region. The sting was removed by the patient. Within hours, erythema, swelling, itching, and pain developed. On day 7, after the bee sting, the patient was admitted to a general surgery department with progressive skin and soft-tissue necrosis around the hip and the upper left leg. Because of the rapidly deteriorating condition, the patient was referred to our burn ICU with the picture of a progressive necrotizing fasciitis. The skin necrosis required immediate epifascial necrectomy. Additionally local therapy with topical antiseptics was performed. The surface was temporarily covered with xenograft, definitive coverage was achieved with autologuous skin graft transplantation. Advancements in wound care and critical care, which have become standard in the treatment protocols of patients with necrotizing soft-tissue infections, have markedly improved the prognosis. However, these infections continue to be a source of high morbidity and mortality and significant healthcare resource consumption. These challenging patients are best served with prompt diagnosis, immediate radical surgical debridement, and aggressive critical care management. Referral to a burn center may help to provide best possible surgical intervention, wound care, and critical care management.

Study on anti inflammatory effect of subcutaneous honey bee venom injection and dermal application of cream containing honey bee venom in adjuvant-induced arthritic rats

Honey bee sting is used in some societies as a treatment of inflammation in joint diseases such as arthritis. To investigate the effect of honey bee venom in reducing inflammation, we selected 30 male Wister rats which were divided in to 6 groups. Except group 1, all remaining groups received 0.5 ml of complete Freund’s adjuvant to induce arthritis. After 9 days, all animals that received adjuvant were suffering from acute inflammation in their joints especially in knee joint (tibia-tarsal region). Group 2 was not received any treatment. Group 3 was received only saline (0.05 ml) by subcutaneous injection at the site of inflammation. Group 4 received cream without any honey bee venom. Group 5 was received cream containing 200μg honey bee venom/gram of cream. Group 6 was received 0.05 ml solution containing freshly prepared 7 μg honey bee venom through subcutaneous injection at the site of inflammation. The parameters determined were, arthritis index score (redness, edema, stiffness in movement) and joint diameter, all the parameters were noted before and during experiment. Results obtained in this experiment shows that all animals that received complete freund’s adjuvant, suffered from acute inflammation, redness and difficulty in movement. Treatment by honey bee venom at mentioned dose could not reduce either the inflammation or difficulty in movement. This study brings a great doubt for using honey bee venom as an anti inflammatory drug.

Pemphigus Vulgaris Induced by Honeybee Sting?

Pemphigus is an autoimmune disease characterized by blistering on the skin and mucosas. The blisters develop due to loss of epidermal cell-to-cell adhesion (acantho-lysis) triggered by auto-antibodies developing against cell surface antigens of keratinocytes. Pemphigus has a chronic progress, with 10% mortality and high morbidity also due to the treatment (1–5).The aetiology of pemphigus is not known exactly. Wide variations in incidence rates, clinical features, and demographic characteristics among countries lead to a suspicion of different risk factors (1).CASE REPORTA 63-year-old male attended beekeeper our clinic with blistering on his whole body. He said he had been stung by hundreds of honeybees on his legs 2 months previously. He had not previously been stung by so many honeybees. He did not have history of allergy to bee venom. The lesions started one month after the bee stings on his legs (on the area of the bee sting) and then spread to his whole body (Fig. 1). On dermatological examination a few erosive lesions were observed on the buccal mucosa and soft palate, and 0.3–3 cm sized, flask blisters and erosive lesions on his extremities and trunk. Some of the blisters had erythematous bases. Laboratory examination did not reveal any patholo-gical findings except an iron deficiency anaemia. No microorganism was isolated from the blister fluids with bacterial culture. Intra-epidermal acantholysis on direct histopathological examination and positive staining with honeycomb-shaped IgG in the intercellular area were observed on direct immunofluorescence examination (Fig. 2). He was therefore diagnosed with pemphigus vulgaris. Corticosteroid (120 mg/day) and azathioprin (150 mg/day) therapies were started orally. His lesions regressed significantly after treatment for 20 days.DISCUSSIONThe aetiology of pemphigus is still not exactly known. A strong association of pemphigus with Class II genes has been demonstrated (4, 6). Some drugs such as D-penicillamine have been reported to induce pemphi-gus. Because there were several reports of pemphigus occurring during pregnancy or with the use of oral contraceptives, hormonal factors have been suggested (7). The potential role of sunlight in the pathogenesis had also been hypothesized, but the mechanism is not clear (1, 4). Environmental factors were thought to be responsible in the aetiopathogenesis of the disease because of its epidemiological features in Brazil and a significant association between pemphigus and frequent exposure to black fly was found in a case-control study (8). Bastuji-Garin et al. (1) investigated patients with pemphigus regarding socioeconomic status, medical history, drug intake, lifestyle, and environment in a multi-centre case-control study in Tunisia. They identified a dose-dependent relationship between pemphigus and traditional cosmetics. In this study, while any associa-tion between exposure to black fly and pemphigus was not found, a significant correlation between wasp, bee and spider stings and pemphigus was also found (1)

Parkinsonism following a honeybee sting

Parkinsonism following a honeybee sting

Acute renal failure following multiple honeybee stings

Hornet stings are medically important stings which can cause allergic manifestations and, in severe cases, may lead to the unusual complication of acute renal failure (ARF) and other systemic complications. ARF results from toxic or ischaemic acute tubular necrosis in a setting of haemolysis or rhabdomyolysis or both and acute allergic interstitial nephritis. Venom from hornet stings can also contribute to myocardial injury or liver impairment. Here, we report three cases of hornet stings leading to ARF. Case #1 and Case #3 recovered their renal function and body physiology after a 38day and 15-day stay in the hospital, respectively, whereas Case #2 died. They were meticulously supported by haemodialysis along with the combination of various drug regimens.

Diagnosis of Hymenoptera venom allergy

The purpose of diagnostic procedure is to classify a sting reaction by history, identify the underlying pathogenetic mechanism, and identify the offending insect. Diagnosis of Hymenoptera venom allergy thus forms the basis for the treatment. In the central and northern Europe vespid (mainly Vespula spp.) and honeybee stings are the most prevalent, whereas in the Mediterranean area stings from Polistes and Vespula are more frequent than honeybee stings; bumblebee stings are rare throughout Europe and more of an occupational hazard. Several major allergens, usually glycoproteins with a molecular weight of 10-50 kDa, have been identified in venoms of bees, vespids. and ants. The sequences and structures of the majority of venom allergens have been determined and several have been expressed in recombinant form. A particular problem in the field of cross-reactivity are specific immunoglobulin E (IgE) antibodies directed against carbohydrate epitopes, which may induce multiple positive test results (skin test, in vitro tests) of still unknown clinical significance. Venom hypersensitivity may be mediated by immunologic mechanisms (IgE-mediated or non-IgE-mediated venom allergy) but also by nonimmunologic mechanisms. Reactions to Hymenoptera stings are classified into normal local reactions, large local reactions, systemic toxic reactions, systemic anaphylactic reactions, and unusual reactions. For most venom-allergic patients an anaphylactic reaction after a sting is very traumatic event, resulting in an altered health-related quality of life. Risk factors influencing the outcome of an anaphylactic reaction include the time interval between stings, the number of stings, the severity of the preceding reaction, age, cardiovascular diseases and drug intake, insect type, elevated serum tryptase, and mastocytosis. Diagnostic tests should be carried out in all patients with a history of a systemic sting reaction to detect sensitization. They are not recommended in subjects with a history of large local reaction or no history of a systemic reaction. Testing comprises skin tests with Hymenoptera venoms and analysis of the serum for Hymenoptera venom-specific IgE. Stepwise skin testing with incremental venom concentrations is recommended. If diagnostic tests are negative they should be repeated several weeks later. Serum tryptase should be analyzed in patients with a history of a severe sting reaction.

Insect Stings

Insect Stings

Tissue Necrosis Following a Honey Bee Sting

Tissue Necrosis Following a Honey Bee Sting

Altered pain-related behaviors and spinal neuronal responses produced by s.c. injection of melittin in rats

Recently, we have reported that following s.c. injection of a solution containing the whole bee-venom (BV; Apis mellifera), into one hind paw of a rat, the experimentally produced honeybee's sting, the animal shows altered pain-related behaviors and inflammation relevant to pathological pain state. To see whether melittin, the major (over 50%) toxic component of the BV, is responsible for the above abnormal pain behavioral changes, the present study was designed to investigate the effects of s.c. melittin on either nociceptive behaviors in conscious rats or spinal dorsal horn neuronal responses in anesthetized rats. In the behavioral surveys, s.c. injection of three doses of both melittin (5, 25 and 50 μg) and BV (10, 50 and 100 μg) into the posterior surface of one hind paw of rats produced an immediate tonic nociceptive response displaying as persistent spontaneous paw flinching reflex. Similar to the BV test, the melittin response was also monophasic and dose-dependent in terms of both intensity and time course. As an accompanied consequence, both heat and mechanical hypersensitivity (hyperalgesia and allodynia) and inflammatory responses (paw swelling and plasma extravasation) were induced by s.c. melittin injections. In the electrophysiological recordings, s.c. injection of the same three doses of melittin into the cutaneous receptive field produced an immediate, dose-dependent increase in spontaneous spike discharges of spinal dorsal horn wide-dynamic-range (WDR) neurons which are believed to be responsible for the spinally-organized nociceptive flexion reflex. The melittin-induced ongoing spike responses are similar to the behavioral flinching reflex in terms of both duration and frequency. Furthermore, the responsiveness of the WDR neurons to both heat (42 °C, 45 °C, 47 °C and 49 °C) and mechanical (brush, pressure and pinch) stimuli was significantly enhanced by s.c. injection of melittin shown as a leftward shift of the stimulus-response functional curves. Taken together, the present results suggest that melittin, the major toxin of the whole BV, is likely to be responsible for production of the long-term spinal neuronal changes as well as persistent spontaneous nociception, heat/mechanical hypersensitivity and inflammatory responses that are produced by experimental honeybee's sting.

An autopsy approach to bee sting-related deaths

Although severe reactions to the sting of the common honey bee (Apis mellifera) are a common problem in Australia, reported deaths are uncommon, with the estimated mortality varying from one to four persons each year. The following study presents the postmortem findings in three cases of bee sting fatality, including one in which no observable sting was found. An autopsy approach to such cases is detailed. Overreporting of bee sting-related deaths may occur due to the inclusion of deaths unrelated to a reaction to bee venom, while under-reporting may be due to unexplained deaths where a history of a bee sting is not available or apparent at autopsy. A classification of bee sting-related deaths is proposed, which would allow more accurate reporting of bee sting-related fatalies. A serum tryptase and specific IgE to bee venom on serum obtained at autopsy can assist in confirming anaphylactic reaction to bee venom as the cause of death, particularly in the absence of observable stings. Although there are limitations to the usefulness of serum tryptase tests in the postmortem situation, it may still be useful to confirm suspected anaphylaxis in autopsy cases with an undetermined cause of death.

Case report of venom immunotherapy for a patient with large local reactions

Inadvertent Hymenoptera stings reportedly elicit large local reactions in up to 17% of the general population. Current practice parameters do not recommend venom immunotherapy (IT) for these cases. The goal of this case study was to investigate the clinical and immunologic consequences of venom IT in a newly sensitized individual with large local reactions using an intentional sting challenge before and after treatment to document changes in reaction severity. A 47-year-old man became honeybee venom (HBV)-allergic with progressively larger reactions at honeybee sting sites with subsequent stings. Then, a sting on his forefinger produced a large (62 cm) local reaction with swelling throughout the arm that persisted for more than 4 weeks with severe pain. He refused steroid therapy and voluntarily requested venom IT with honeybee-sting challenges to monitor clinical parameters and immunologic changes in his skin and serum before and 7 months post-HBV maintenance IT. A single pre-IT bee sting challenge produced an 11.4-cm wheal with 13-cm erythema at the sting site after 15 minutes, followed by several weeks of edema that involved the entire arm. After rapid escalation of venom IT to maintenance in 7 weeks, a post-maintenance IT sting challenge with two honeybees produced a 3-cm diameter erythema with no wheal at 15 minutes and no late-phase induration. Complete loss of any visible reaction at the field sting site resulted after 13 months of maintenance venom IT. A HBV-specific IgG antibody level >3.5 microg/mL and IgG/IgE antibody molar ratio >500 persisted over the period of venom IT, with venom skin reactivity diminishing 100-fold. These results support venom IT use in the treatment of Hymenoptera venom-sensitive individuals who experience large local reactions and are at risk for repetitive inadvertent stings.

Does Honey Bee Sting Alarm Pheromone Give Orientation Information to Defensive Bees?

We tested compounds found in honey bee, Apis mellifera L., sting alarm pheromone for their roles in releasing behavioral responses, with a focus on the relative importance of chemotaxis and motion of the target in the localization response. Some compounds in the blend have specialized functions. Benzyl acetate released only flight behavior, whereas three compounds (1-butanol, 1-octanol, and hexyl acetate) caused only the recruitment response. Other compounds (1-hexanol, butyl acetate, iso-pentyl acetate, and 2-nonanol) acted in more than one behavioral context. Octyl acetate was the most effective compound in allowing bees to locate targets, but did not recruit or release flight behavior. Stationary octyl acetate sources were located by flying bees, indicating that this pheromone component elicits a chemotactic response. However, localization of a target is due primarily to the motion of the target; the alarm pheromone components release searching behavior for a moving object and are relatively unimportant in target localization.

Induction of the Split Sting Trait in Africanized Apis mellifera (Hymenoptera: Apidae) by Cold Treatment of Pupae

Split sting is the name given to a nonfunctional honey bee sting characterized by lancets not attached to the stylet. It has appeared in a mutant line in Brazil, and has provoked interest as a possible means to reduce honey bee colony defensiveness. We induced this alteration in Africanized Apis mellifera L. workers and queens by maintaining pupae at 20°C. In particular, we determined the pupal phase most susceptible to alterations in the sting caused by cold treatment, and we investigated whether this treatment also affected survival to the adult phase and wing morphology. The highest frequency of split sting was detected in workers treated at the pink-eyed pupal phase. The lowest frequency was observed in the bees treated at the oldest worker pupal phase studied (brown-eyed pupae with lightly pigmented cuticle). Both queen pupal phases tested (white and pink-eyed pupae) were equally sensitive and produced high percentages of adults with split sting. However, the 20°C treatment of workers and queens, at the different pupal phases, resulted in high frequencies of adults with deformed wings. Also, fewer workers and queens treated at the earlier pupal stages reached adult emergence. There was also an arrest in developmental time, corresponding to the period of cold treatment.

Bee sting allergy in beekeepers.

Beekeepers are strongly exposed to honey bee stings and therefore at an increased risk to develop IgE-mediated allergy to bee venom. We wondered whether bee venom-allergic beekeepers were different from normally exposed bee venom-allergic patients with regard to clinical and immunological parameters as well as their response to venom immunotherapy. Among the 459 bee venom-allergic patients seen over the 5 year period 1987-91, 62 (14%) were beekeepers and 44 (10%) family members of beekeepers. These two groups were compared with 101 normally exposed bee venom-allergic patients matched with the allergic beekeepers for age and sex, regarding clinical parameters, skin sensitivity, specific IgE and IgG antibodies to bee venom as well as safety and efficacy of venom immunotherapy. As expected, allergic beekeepers had been stung most frequently before the first allergic reaction. The three groups showed a similar severity of allergic symptoms following bee stings and had an equal incidence of atopic diseases. Allergic beekeepers showed higher levels of bee venom-specific serum IgG, lower skin sensitivity and lower levels of bee venom specific serum IgE than bee venom-allergic control patients. A negative correlation between number of stings and skin sensitivity as well as specific IgE was found in allergic beekeepers and their family members, while the number of stings was positively correlated with specific IgG in these two groups. Venom immunotherapy was equally effective in the three groups, but better tolerated by allergic beekeepers than the two other groups. The majority of allergic beekeepers continued bee-keeping successfully under the protection of venom immunotherapy. The lower level of sensitivity in diagnostic tests and the better tolerance of immunotherapy in allergic beekeepers is most likely related to the high level of specific IgG in this group.