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- Venom -
3/11/04 re: Venom immunotherapy I have a 54 year old patient with a history of reactions to hymenoptera stings. She has had several reactions. One reaction, 10 years ago, caused her to have loss of consciousness. Her last reaction was 2 yrs. ago with rash, SOB and lightheadedness - for which she used her epi-pen and went to the ER. She was begun on IT to wasp and mixed vespid in 2/03. Since then she has had several reactions to IT. These involve lightheadedness, weakness and nausea with a feeling as though she is going to faint. Her BP and pulse remain normal and her lungs are clear. She has been treated with benadryl and occ. epi. For this in my office with rapid resolution of symptoms. The problem is that I have only been able to get her to 10 ug of wasp and 30 mg of mixed vespid. She usually comes for shots once a week. Any hints on how to safely advance her? Would taking an antihistamine prior to IT be helpful or giving only 1 shot per visit?
Enclosed is the input I obtained from Dr. Robert Reisman of SUNY Buffalo, a highly regarded expert in venom sensitivity and associated immunotherapy.
Reply to insect question:
The described reaction related to VIT has clinical features of a vaso-vagal reaction rather than a true allergic reaction. Further information which might be helpful:
- any reaction at site of VIT
- results of venom tests
-any similar reaction related to other injections or blood drawingWould suggest:
- administer one injection per visit, attempting to raise dose of most important suspect venom
- do not believe antihistamine prior to VIT helpful and may actually confuse issue
- have patient lie down when injection given.5/21/02 re: Venom immunotherapy for a child? A nine year old boy was stung "three times" on his finger and hands by an insect that came out of the ground and "looked like a yellow jacket". About 45 minutes later, he was noticed to develop progressive angioedema and urticaria. The angioedema was of his lips, and did not seem threaten his airway. He had giant diffuse urticaria. His heart rate was 88/min., and there were no breathing problems. He did not have cough or wheezing. When he was taken to his family practitioner's office, the physician and nurse were "alarmed" and took him to the treatment room immediately. There was some discussion at the time about whether he was in "early shock" - but he never had tachycardia, and he improved immediately with administration of epinephrine.
Venom skin tests revealed 2-3+ reactions to intradermal tests with 0.1 mcg/ml for yellow jacket, and 0.1 mcg/ml for bald faced hornet. The physician now (8 months later) reports he did not feel there was any shock. I have read the information regarding indications for venom immunotherapy - and felt that its application is not clear-cut in this case - perhaps due to the boy's "alarming" presentation, and the suggestion that his symptoms might have gone beyond cutaneous manifestations. Is there an argument that one could muster to help his parents decide about venom immunotherapy?
As you are likely aware, Golden and colleagues in Johns Hopkins had concluded some time ago that venom immunotherapy was not needed in hymenoptera-sensitive children who had exhibited only cutaneous manifestations to a previous field sting. They had found only a 1-10% risk of systemic anaphylaxis during a repeat sting in such individuals (see enclosed abstract). Unfortunately, it has been subsequently found that the levels of specific IgE anti-venom antibodies or the size of the venom skin test reaction was not a reliable predictor whether a child in this group would be one of the minority who would manifest a more severe systemic reaction to a repeat sting. In the case of your patient, where there is a question of whether there was more than cutaneous manifestations following the prior sting, I would lean towards recommending venom immunotherapy particularly if: 1) the child's activities put him at a reasonable risk for being restung; 2) it appears unlikely that the patient would be compliant with epinephrine self-administration; 3) there is sizable concern in the parents about the possibility of a serious systemic reaction to a future sting. It should be explained to the parents that venom immunotherapy must be continued for at least 3 (and possibly 5) years and is not always completely protective, although those systemic reactions to re-stings in those on immunotherapy are usually much milder (see enclosed abstract). In a borderline case such as this, I think that it is particularly important for the parent to sign a carefully and clearly worded informed consent document whether the parents elect to have venom immunotherapy in their child or not.
Allergy Proc 1989 Mar-Apr;10(2):103-7
Epidemiology of allergy to insect venoms and stings.
Golden DB.
Johns Hopkins University School of Medicine, Department of Medicine, Good Samaritan Hospital, Baltimore, Maryland 21239.Stings by bees, yellow jackets, hornets or wasps may cause allergic reactions in sensitized individuals, including systemic or anaphylactic reactions. The epidemiology and natural history of insect venom allergy is emerging in the past decade and has clarified the reasons for the false perceptions that whole body extracts of the insects were considered effective for therapy. Up to 3% of adults have had a systemic sting reaction but 25% show venom sensitivity on skin test or RAST. Sensitization is common after a sting but is transient in 50% of cases. The risk (and pattern) of systemic reaction differs in children, but is 50% for those with positive history and skin test. Lower risk of reaction is expected in those with positive skin tests and large local reactions (5-10%), no previous reaction (10-20%), children with strictly cutaneous generalized reaction (1-10%), or for those with no stings for over ten years (15-25%). These observations have profound impact on the evaluation of patients for initiation or discontinuation of venom immunotherapy.
Curr Opin Allergy Clin Immunol 2001 Aug;1(4):353-6
Discontinuing venom immunotherapy.
Golden DB.
Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland 21224, USA.The decision to discontinue venom immunotherapy requires a great deal of clinical judgement because of the potential for a life-threatening reaction to a sting. The risk of recurrence is a combination of the frequency of reaction and the severity of reaction. Early studies reported a relapse rate of 8-14% in radioallergosorbent test-negative patients when therapy was stopped after 3 years. Unfortunately, the venom skin test or radioallergosorbent test becomes negative in only 25% of patients after 5 years of treatment. An alternative criterion for stopping treatment after 5 years regardless of the skin test has been equally successful, with most post-treatment reactions being much milder than pre-treatment reactions. There was no evidence of a rebound of venom sensitivity when therapy was stopped, even when patients were stung. The level of venom-specific IgE antibodies is better suppressed by 5 than by 3 years of treatment. The risk of relapse is higher in honeybee-allergic patients and in patients who had a systemic reaction (to a sting or an injection) during therapy. The frequency of reaction may be low, but patients who had very severe pre-treatment reactions have a greater chance of the reaction being severe again, and should remain on therapy for life. Long-term observations show that the incidence of systemic reaction to a sting remains 10% for each sting that occurs, even 10-15 years after stopping treatment. Because patients may not react to one sting and then subsequently react to another sting, the cumulative frequency of sting reactions is approximately 17% after 10 years off treatment. Moreover, negative venom skin tests are not a guarantee of safety because there is almost the same 10% frequency of reaction in patients who appear to lose sensitivity. It is not yet clear whether some low-risk patients (children, mild reactors) could discontinue treatment after just 3 years.
5/31/01 re: Value of ingested bee pollen
Has there been any research done on the use of bee pollen to help people desensitize their allergies? I am aware of lots of testimonials and lots of groups that sell bee pollen, but I am talking about solid, scientific research. It would make some sense that it could work since a person would be ingesting small amounts of the substances much like immunotherapy, but as an MD, I would like to base any recommendations on real research, and not just hearsay. It is not clear from your question whether you wondered whether ingested bee pollen would specifically desensitize bee-venom-sensitive individuals to the venom allergens or act as a broad based desensitizing agent against all allergens. As you may know, ingestion of bee pollen or "royal jelly" obtained from bee hives has been recommended by enthusiasts for a whole variety of human ailments (see enclosed abstract by Greenberger et al). There is little, if any, scientific evidence from controlled studies to show efficacy of these products. Furthermore, there have been reported cases of severe allergic reactions to ingested bee pollen or royal jelly in individuals very sensitive to either the bee venom of plant components that become part of the bee pollen. Therefore, I think that ingestion of bee pollen is unlikely to be helpful and may actually trigger allergic reactions rather than desensitize. I have enclosed some relevant abstracts for your interest Ann Allergy Asthma Immunol 2001 Feb;86(2):239-42
Bee pollen-induced anaphylactic reaction in an unknowingly sensitized subject.
Greenberger PA, Flais MJ.
Division of Allergy-Immunology and the Ernest S. Bazley Asthma and Allergic Diseases Center of Northwestern Memorial Hospital and Northwestern University Medical School, Chicago, Illinois 60611-3008, USA.Background: The food supplement bee pollen has been previously found to cause anaphylactic reactions. It has been proposed as useful for "everything from bronchitis to hemorrhoids."
Objective: This study describes an atopic patient who experienced a non-life-threatening anaphylactic reaction upon her initial ingestion of bee pollen. Microscopic examination of the pollen sample and ELISA inhibition assays were performed.
Results: The patient had a 7 mm/28 mm wheal/erythema reaction to bee pollen at 1 mg/mL concentration. Bee pollen caused 52% inhibition of IgE binding to short ragweed and 55% to ryegrass. Microscopic analysis revealed ragweed, Alternaria, Cladosporium, honeysuckle (Lonicera sp), privet shrub (Ligustrum sp), and vetch (Vicia sativa).
Conclusions: An unknowingly sensitized atopic patient experienced an anaphylactic reaction after ingestion of a small quantity of bee pollen that contained pollens and fungi. Previously administered allergen immunotherapy that had reduced rhinitis symptoms did not prevent this allergic reaction.J Am Board Fam Pract 1994 May-Jun;7(3):250-2
Anaphylactic reaction after ingestion of bee pollen.
Geyman JP.
Inter-Island Medical Center, Friday Harbor, Washington.Bee pollen allergy, although relatively rare, can present a life-threatening medical emergency. Conventional treatment of anaphylaxis is indicated, and further allergic workup is not necessary. There is little awareness of this hazard among the general population. Warnings to include product labeling of potential adverse reactions in sensitive individuals are urgently needed to protect the public from this hazard.
Allergol Immunopathol (Madr) 1998 Nov-Dec;26(6):288-90
Allergic reactions to honey and royal jelly and their relationship with sensitization to compositae.
Lombardi C, Senna GE, Gatti B, Feligioni M, Riva G, Bonadonna P, Dama AR, Canonica GW, Passalacqua G.
Dept. of Internal Medicine Sant'Orsola Hospital, Brescia, Italy.Honey and royal jelly are complex etherogeneous mixtures of flowers' nectar, sugars, proteins and bee's glandular secretions. The existence of a type I hypersensitivity to honey is still matter of debate, while an aetiological role of Compositae pollens in the clinical manifestations following honey ingestion has been envisaged. We describe two cases of severe systemic reactions (anaphylaxis and generalized urticaria/angioedema) due to honey and royal jelly ingestion in patients sensitized to compositae (mugwort). Both patients had a skin and RAST positivity to mugwort and a positive prick-by-prick to the offending foods. Moreover, in one of the two patients the RAST-inhibition assay showed the strong cross-reactivity between the proteins of honey and mugwort and the SDS-PAGE analysis showed that the major proteic bands from honey and mugwort extracts are largely superimposable. Both the clinical data and the laboratory analysis support the hypothesis of a strict link between sensitization to compositae and adverse reactions to honey and jelly.
Clin Exp Allergy 1997 Mar;27(3):333-6
Royal jelly consumption and hypersensitivity in the community.
Leung R, Ho A, Chan J, Choy D, Lai CK.
Department of Medicine, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, Hong Kong.Background: Royal jelly consumption has recently been linked with acute asthma, anaphylaxis and death. A cross-sectional survey was conducted to determine the prevalence of and the relationship between royal jelly consumption and hypersensitivity reactions.
Methods: 1472 hospital employees of a teaching hospital in Hong Kong completed a questionnaire on royal jelly consumption and related allergic symptoms, and 176 questionnaire respondents and 300 consecutive asthma clinic patients were skin tested to royal jelly.
Results: Royal jelly consumption was high, with 461 out of 1472 subjects (31.3%) having taken royal jelly in the past. A total of nine subjects reported 14 adverse reactions to royal jelly, including urticaria, eczema, rhinitis and acute asthma. Thirteen out of 176 questionnaire respondents (7.4%) and 23 out of 300 consecutive asthma clinic attendees (7.3%) had positive skin test to pure royal jelly. All but one of the 36 subjects with positive royal jelly skin test were atopic to other common allergens. Positive associations were found between positive royal jelly skin test and atopy (OR = 33.73, 95% CI 4.51 to 252.11), adverse reactions to royal jelly and a history of clinical allergy (OR = 2.88, 95% CI 0.72 to 11.58), but not between royal jelly symptoms and previous royal jelly intake.
Conclusion: Royal jelly consumption is high in the community of Hong Kong. Atopic individuals are at high risk of sensitization to royal jelly but the precise relationship between royal jelly use, positive royal jelly skin test and clinical manifestations of adverse reactions to royal jelly, remains to be defined.5/29/01 re: Sensitivity of skin test vs RAST for venom allergy What are the relative merits of skin testing and RAST testing for insect sting allergy? Based on earlier studies, the usual clinical practice has been to consider individuals who exhibit negative skin test responses to a panel of the currently available hymenoptera venom extracts to be at no significantly increased risk for a systemic reaction to a subsequent sting. This was thought to be the case even in individuals who gave a fairly convincing history of a systemic reaction to a previous sting. However, the recent report by Golden et al (which you may have seen) indicates that about 20% of their "history positive/skin test negative" individuals manifested a systemic reaction to a sting challenge. In some of these individuals there had been evidence of serum IgE antibodies against one or more venom allergens by their sensitive in vitro immunoassay. I have enclosed below a review of their report which I wrote for the Current Literature section of this AADMC website.
The Insect Committee of the AAAAI, including Dr. Golden, is in the process of writing a committee report which should include recommendations in this area.
Insect sting allergy with negative venom skin test
Summary
There have been reports of individuals with histories of severe systemic reactions to hymenoptera insect stings despite being skin test negative to the relevant venom. Golden et al of Johns Hopkins University in Baltimore, MD prospectively examined the prevalence of negative venom skin test responses in 307 patients with positive histories of systemic hymenoptera sting reactions. In 99 (32%) of these patients, venom skin tests up to 1 microgr/ml were negative. In 36 of these 99 patients there were low positive venom in vitro (RAST) tests. Occasionally a repeat venom skin test was positive. In another 7 of the 99, high levels of anti-venom IgE antibody were found in the RAST tests. Sting challenges were performed in 141 of 196 patients with positive venom skin tests, resulting in 30 systemic reactions. Sting challenges in 37 of 43 patients with negative skin tests and positive venom-specific RAST tests elicited systemic reactions in 9 individuals. Sting challenges in 14 negative skin test/negative in vitro test subjects elicited systemic reactions in 2 individuals. The authors concluded that negative venom skin test responses can be seen in some individuals with convincing histories of systemic reactions to field stings. The serum of some of these subjects contains venom-specific IgE, as detected by a sensitive RAST. Up to 24% of the venom skin test-negative subjects will manifest a systemic reaction to a sting challenge. Better skin testing reagents are required.Reference
J Allergy Clin Immunol 2001;107:897-901Editor's Comments
For years, most clinicians have been assured that patients with histories of apparent systemic reactions to a previous hymenoptera insect sting but now venom skin test negative are not at increased risk for a systemic reaction to a subsequent sting. The findings described above by one of the most experienced groups investigating venom sensitivity are therefore quite disturbing. Screening venom skin testing, using currently available reagents, is not apparently sensitive enough to detect all systemically sensitive individuals. Indeed, the percentage of these patients with negative venom skin tests who subsequently reacted to a sting challenge was not that much different than the percentage of venom-skin-test-positive individuals who reacted to a sting challenge. Is there anyway that one can increase the sensitivity of the venom skin testing procedure used in clinical practice? One could try skin testing with higher concentration venom extracts in individuals with convincing histories of sting systemic reactions who exhibit negative skin test responses to the top concentration of 1 microgram/ml of venom extract currently recommended. However, there are a sizable number of false positive skin test reactions to such venom concentrations greater than 1 microg/ml. The in vitro tests used by Golden et al may increase the sensitivity of screening approaches but they are research lab procedures not necessarily paralleled by the RAST-type assays used in commercial clinical labs. Obviously, improved approaches are needed.11/29/00 re: Serum sickness reaction to hymenoptera Do you think that serum sickness-like reactions to hymenoptera warrant immunotherapy? I read in middleton that they can be associated with ANA, but that shots aren't indicated for this type of mechanism. There have been scattered reports of serum sickness type reactions starting days after a hymenoptera sting. It is generally felt that a history of such reactions are not, by themselves, an indication for hymenoptera venom immunotherapy. I have enclosed below my response to a previous Ask the Expert question in this general area. However, occasionally patients with such histories will exhibit immediate skin test reactivity to low concentrations of the relevant venom allergen. I have personally followed one patient with this pattern who could not accept the idea that she might be at increased risk for an immediate systemic reaction from a repeat hymenoptera sting. She was stung by a similar insect one year later with a resultant anaphylactic reaction, fortunately not severe.
Therefore, if skin test with relevant venom allergens shows very strong immediate reactivity, I would at least prescribe strict avoidance measures and carrying self injected epinephrine syringe with suitable instructions. Also consider immunotherapy.
Late onset (after 4 hours) systemic reactions to hymenoptera stings occur only very occasionally. For example, in the cooperative survey study carried out by the Insect Committee of the American Academy of Allergy, Asthma and Immunology, only about 1% of the systemic reactions started more than 4 hours after the sting. In my previous conversations with Dr. Robert Reisman, an expert in hymenoptera sting reactions (and who wrote one of the first reports about such delayed onset reactions,) he did not recommend IT if there was no evidence of an IgE-mediated reaction.
11/7/00 re: Approach to fire ant sensitivity in an infant I had a 16 month old patient who was had fire ant bite and developed swelling of the face hand coughing and wheezing. This was treated by the aunt (who regularly baby sits the child) with benadryl and symptoms subsided. Epipen jr was prescribed and ant avoidance was instructed. In view of child's age ,at what age allergen immunotherapy should be considered as there is also risk of anaphylaxis due to immunotherapy and at 16 months of age is that risk appropriate? Since I have no personal experience with fire ant allergy in this part of the USA, I consulted Dr. Richard Lockey of the Univ. of S. Florida, an expert on this area of study His response about your case is: This is a catch twenty-two situation. The child seems to be allergic and definitely should have epinephrine available for injection by a parent or other designated individual. You have the choice of:
1) explain to the parents that very few children with this sort of problem die from anaphylaxis and to carry and use the epinephrine whenever necessary
or
2) to obtain skin tests or RAST test or both in the child and then explain the option of immunotherapy vs the other. approach Carefully document everything in writing for medico-legal reasons
I favor the latter approach to document and show the family there is a potential problem. She will be positive. Here in Florida it is possible to avoid fire ants only if one stays inside--not practical as the child ages. I would start immunotherapy if the child is sensitive to fire ants and if everyone is in agreement.
3/24/00 re: fire ant sting When a child is bitten by fire ants...small amount...how long must you look out for an allergic reaction? Fire ants stings are similar to the sting from any other animal in the Hymenoptera family (in which fire ants, bees, wasps, etc are members). Sting reactions usually begin within the first hour following a sting and almost always with 2 hours. There are exceptions and some have occurred hours after. So I would say that two hours are the rule and you cannot worry about the rare cases in which it is longer. If reactions do occur later than two hours they are rarely if ever life threatening. Hope this helps and good luck. Dick Lockey, Professor, University of South Florida College of Medicine, Tampa, FL. Please access: http://homepages.go.com/~jaynedye/event.html to read the clinical case report and my questions concerning a 9 yr. old male patient with a life-threatening reaction to 'some bite/sting'. First, I should compliment you about your excellent case description on your website. You can be proud of it. You also have been thinking incisively about this unusual and puzzling case. I am also not aware of well documented anaphylactic/anaphylactoid reaction to spider venoms. I could not find evidence for this in several review articles listed below. The impressive metabolic acidosis (without apparent compensating blowing off of CO2) in your case raises the possibility of the systemic effect of some injected toxin. The marked loss of plasma from the vascular compartment is not unusual in anaphylaxis, sometimes without apparent interstitial edema. Large volume of replacement fluids may be required to restore blood pressure to normal.The mental changes in your patient could be due to cerebral edema and/or hypotension effects. The past history of an urticarial reaction to a wasp sting is not that helpful since there does not appear to be that much protein homology between the venom of spiders and that of the hymenoptera which commonly induce allergic reactions (vespids, bees).
Proving your thesis of an allergic reaction to spider venom will be difficult. If you could convince an expert investigator to set up a RAST-type assay to measure IgE antibodies against the funnel web spider venom (with suitable controls), this might help provide evidence.
12/6/99 re: Information regarding treatment of reactions to yellow jackets I would like information about treatment of ALLERGIC RESPONSES to yellow jacket (Vespulus germanicus) puncture. Space limitations do not allow the extensive responses required for the very general question posed. I will make some brief comments and suggest that you also refer to other questions about this subject in this Ask the Expert section and to reviews in the Current Literature Section for more information.
- First, one must determine that the reaction to the yellow jacket (YJ) sting was truly allergic. Large local non-allergic reactions to the venom injected occur commonly at the sting site. However, generalized urticaria/asthma/anaphylaxis strongly suggest an allergic reaction. Consultation with an allergist and appropriate skin testing will be of great assistance.
- If the individual had an allergic reaction, I use a combination of 3 approaches.
a. Avoidance measures (e.g. avoid barefeet/sandals/certain clothing colors/perfumes when in areas populated by YJ).
b. Carry tourniquet and epinephrine self-injection for urgent use in case of a YJ sting.
c. Strongly consider YJ venom immunotherapy. This is a highly effective preventive measure but will require the consultative assistance of a trained allergist.10/13/98 re: treatment of post-herpetic neuralgia and I was asked by a patient about bee pollen injections for postherpetic neuralgia and could not find much in the literature search. I think this is one of those unproven alternative therapy, but can you confirm that? This patient has tried Neurontin, Valtrex, Capsaicin, etc., without much relief. He also asked about whether Varicella vaccine could help his pain. He is 73-year-old male with persistent typical dermatome area pain without rash for over three years, and has been to neurologist, pain management, etc.
I also know of no value of bee venom injections for post-herpetic neuralgia. As you know, the latter condition is very difficult to treat successfully. I know of no evidence showing value of varicella vaccine. Contradictory findings have come from studies of corticosteroid therapy which generally has been used soon after appearance of the neuralgia. Some investigators report success with the use of tricyclic anti-depressants, presumably by impairing inter-nuncial pain conduction.Other therapies to consider in severe, persistent post-herpetic neuralgia include ketamine and topical capsaicin (rubbed in over the involved dermatome cautiously, starting with a small amount). I think that the latter is marketed as Zostrix cream. 8/14/98 re: resuming venom immunotherapy I have an extremely allergic patient to pollens, molds, environmentals and insect venoms. She has received allergy shots for six years for these, stopped shots, and a year and a half later, she wishes to resume shots due to increased allergy symptoms. She had six years of venom immunotherapy to all 5 venoms. She has not been stung in the last eight years. Stings in the past caused large local reactions and concomitant nausea and "feverishness". I have decided to not resume venom immunotherapy on her. Do you agree? Would you do any diagnostic work up (re-skin test for example) in order to modify the decision? The best, succinct summary of current knowledge in response to your question is contained in a report of the experts comprising the Insect Venom Committee of the AAAAI ( published in the J Allergy Clin Immunol 1998;101:573-75). I have tried to summarize their recommendations in the review "Discontinuing Venom Immunotherapy" in the Current
Literature Section of this AADMC website.
