Although it’s part of the business, few of us actually look forward to being stung. As beekeeperswe need to know about the various reactions to bee stings and be responsible to ourselves, family, neighbors and friends in regard to bee stings. I hope this article will serve some of thosepurposes and be informative to both the beginner beekeeper and the most experienced. The firstpart of this article covered insects that sting, honey bee stings in particular, basic bee venom biochemistry, precautions and sting prevention, management of beekeeping emergencies, andbasic immunology and allergy. This second part will cover sting reactions and types, sting treatments, allergy testing and desensitization results, and specific beekeeper recommendations.

Sting reaction types and treatments

The NORMAL reaction to a ven-omous insect sting is one of localpain and up to a few centimeters of

edema (swelling) that resolves in a fewhours to a few days (Figure 10). Any stingcan become secondarily infected, but for-tunately, this is fairly uncommon.Parenthetically, fire ant stings form apseudopustule (Figure 11). These blistersmay last for 10 days and should not beconfused with a true infection (pustule).The pseudopustules from fire ant stingsshould be left intact (not unroofed or surgi-cally drained).

The first ‘treatment’ of a normal reac-tion is to quickly remove the sting andsmoke the area. Many local remedies havebeen suggested for the treatment of beestings. These generally fall into 4 cate-

gories: 1) venom removal or suctiondevices, 2) bases such as urea, ammonia,and baking soda (to neutralize the acidityof the venom), 3) hygroscopic agents (todraw out the fluid) such as honey, mud,and various pastes, and 4) lotions todecrease the itch such as calamine lotion,Anusol, and Benadryl cream. All topicaltreatments require immediate application,so they are probably best used in non-bee-keeping situations. And as far as localapplications for sting prevention is con-cerned, DEET-containing bug sprays donothing to deter vespid stings. Normalreactions are not an allergic response, andallergy testing and desensitization are notindicated after these.

A LARGE LOCAL reaction is confinedto the general area of the sting, but over 24– 48 hours it develops into a much larger

area (sometimes the entire extremity) thana normal reaction (Figure 12). It starts aspain and a wheal (a several centimeterswollen itch). A few hours after the stingmore redness, edema (swelling), and itch-ing develop. Over 12 – 48 hours, the areacan become quite swollen, painful, andmay also have some associated ecchymo-sis (flecks of purple or red from a bruisewithin the skin itself). The swelling gener-ally begins to resolve after two days, butthe site may remain tender (and continue toitch) for a few more days. The total reac-tion lasts 4 – 7 days. Large locals aroundthe face and mouth or on the hands maycause temporary disability. The large localis IgE-mediated, and therefore is an aller-gic response.

Treatment of a large local includes iceand elevation. Taking an anti-histamine or

by BUDDY MARTERRE, MD

Part II of Two Parts

Figure 10. Normal Sting Reaction of Face Buddy Marterre, MD

Figure 11. Pseudopustules of Arm fromFire Ant Stings Courtesy of Murray SBlum

Marterre article Bee Stings part 2.qxp 7/13/2006 2:42 PM Page 1

a leukotriene-receptor antagonist verysoon after the sting may decrease the latephase reaction. Personally, this is what Ido and it works for me! Oral steroids areuseful in treating large locals to stingsaround the face and hands. Anti-Histamine choices are sedating drugs suchas diphenhydramine (Benadryl), and non-sedating ones, such as fexofenadine(Allegra), loratidine (Claritin), and ceter-izine (Zyrtec). Benadryl and loratidinemay be obtained without a prescription(over the counter). Caution is advised withdriving (or continued beekeeping) aftertaking a sedating anti-histamine (particu-larly if high doses are taken), however.Oral steroids in the form of prednisoneshort courses and dose packs require eval-uation by a physician and prescription. Asmentioned above, another class of pre-scription drugs that may help are theleukotriene-receptor antagonists mon-telukast (Singulair) and zafirlukast(Accolate). These drugs block theleukotriene receptors on mast cells andeosinophils and both have peak activity 3– 4 hours after taking them. People whohave (only) had a large local response,have little or no risk of a severe, life-threatening anaphylactic response in thefuture. Therefore, even though a largelocal reaction is an allergic response,allergy testing and desensitization are notindicated after these.

SYSTEMIC ALLERGIC responsesinvolve two or more organ systems ofthe body and are called ANAPHYLAX-IS. They can be mild and manifest aspurely cutaneous (skin) responses, ormay include symptoms of the gastroin-testinal system or nervous system, orworse, the cardiorespiratory systems. Asystemic cutaneous (or skin) responsemust be distant from the sting site (todifferentiate it from a large local reac-tion) and typically involves the trunk orscalp. Generalized cutaneous responsesinclude urticaria or hives (the familiar,itchy 5 – 40 millimeter red wheals andslightly raised flares – Figure 13) and/orangioedema (a rapidly-developing mas-sive swelling of the face – Figure 14).Gastrointestinal symptoms include ametallic taste, nausea, vomiting, diar-

rhea, and abdominal cramps. Neurologicsymptoms include light-headedness,dizziness, and tremor, but light-headed-ness and dizziness can also be due to adrop in blood pressure, which would be acardiovascular effect.

Fortunately, cardiorespiratory systemresponses (severe ANAPHYLAXIS) occurin less than 1 % of people incurring a beesting. Anaphylaxis may be preceded bygeneralized itching, hives, and edema, andthe specific cardiovascular and respiratorysystem reactions can progress fairly rapid-ly (over 1 to 30 minutes). They includewheezing, stridor (airway compromise andinability to breathe), shock (very lowblood pressure causing collapse), loss ofconsciousness, and death. Beekeepers,family members (or anyone) who has hada moderate or severe systemic allergy to

bee stings should see an allergist for skintesting and immunotherapy.

Anaphylaxis to insect venom accountsfor about 40 deaths per year in the US.About 40 % (or about 16) of those areattributable to honey bees, but this may bean underestimate (due to some un-wit-nessed venom-related deaths being falselyattributed to heart attacks). In comparison,lightning strikes account for about 85, ani-mal bites 100, poisonings 3,600, smokingover 150,000, and cancer almost 500,000deaths per year in the US!

The treatment mainstay of anaphylaxisis intramuscular epinephrine (Figure 15).Dose depends on size. Children that weighless than 30 kilograms (66 pounds) need anEpiPen Jr (0.15 mg) and larger childrenand adults need a ‘regular’ EpiPen (0.30mg). In either case the injection is givenfrom the one-time-use pre-filled adminis-tration syringe into the anterolateral thighand may (and sometimes should) berepeated every five minutes en route to anemergency room. There is also a new epi-nephrine injector called TwinJect, whichcan deliver two injections, but requirespartial disassembly between injections.EpiPens and the TwinJect device require aprescription as there may be some risk toadministering epinephrine to someonewith severe heart disease. EpiPens comewith ‘practice’ administration syringes andinstructions. If you, anyone in your family,or the neighbors to your bee yard have asystemic allergy, have at least one epineph-rine injector on hand and know how to useit! Other treatments for anaphylaxisinclude bronchodilator inhalers (prescrip-tion), and anti-histamines and steroids - asfor large local reactions. Anyone experi-encing anaphylaxis (epinephrine-treated ornot) needs to be transported directly to anemergency room. Most of these patientswill be admitted to the hospital overnightas sometimes the reactions recur (typicallyat 4 – 6 hours). Remember those secondarychemicals that the mast cells make thatcause the late phase of allergy? Allergytesting and venom immunotherapy desen-sitization is indicated for anyone with asystemic allergic response to insect stings,including diffuse hives in anyone over 16years of age. Allergy testing is not recom-

Figure 12. LargeLocal Reaction ofHand and Wrist

Buddy Marterre, MD

Figure 13. Urticaria or Hivescourtesy of Dr. Raymond J. Mullins,

allergycapital.com.au

Figure 14. Facial Angioedema Same patient, before and after treatmentcourtesy of siamhealth.com

Marterre article Bee Stings part 2.qxp 7/13/2006 2:42 PM Page 2

mended for urticaria / hives alone in achild (under 16).

MASSIVE ENVENOMATION (some-times called a toxic reaction) occurs withgreater than 500 honey bee stings. This isnot an allergic response, but is related tothe large amount of venom received by thevictim. Very young children or chronicallyill elderly people may be poisoned by 150(or more) stings. The ‘dose’ of bee stingsthat has been calculated to kill half of thevictims (LD50) is 19 stings per kilogramof body weight. Initial symptoms of beevenom toxicity include generalized edema(swelling), fatigue, nausea, vomiting,fever, and unconsciousness. The reaction issometimes delayed by as much as 6 daysand therefore requires immediate trans-portation to an emergency room and hospi-talization. The problems are primarily theresult of rhabdomyolysis (breakdown ofmuscle tissue) and myoglobinuria (themuscle breakdown products in the bloodleading to kidney failure). Hemolysis(burst red blood cells), DIC or disseminat-ed intravascular coagulation (abnormalclot formation inside the blood vesselswith an overuse of clotting factors and sub-sequent bleeding) can also occur. Kidneyfailure and cardiac arrest cause most toxicbee sting deaths (which are considerablyrarer than anaphylaxis deaths).

OCULAR (or eyeball) STINGS are for-tunately quite rare (because of theextremely fast human blink response), butwhen they do occur they frequently lead toblindness. Immediate attention by an oph-thalmologist is warranted. Specific ocularsting injuries include corneal edema,hyphema (blood in the anterior chamber ofthe eye), lens dislocation, cataract, andoptic neuritis (inflammation of the opticnerve). Prevention is clearly the key tothese injuries. Veils only cost a few dollarsand can be donned in seconds! Table 6summarizes venom reaction types andtreatment.

Allergy testing and desensitizationAlthough large local reactions are aller-

gic responses, allergy testing and desensi-tization immunotherapy are not indicatedafter these because the risk of a severe sys-temic reaction to re-sting is extremely low.People who have experienced a systemicallergic response (including urticaria ordiffuse hives in someone over 16) certain-ly benefit from allergy testing and subse-quent desensitization immunotherapy.Desensitization venom immunotherapy(allergy shots) is warranted in anyone whohas had a systemic reaction and in whom

the risk of a systemic reaction with re-stingis 20 % or greater and has also had a posi-tive skin test to the venom. Skin testing ismore sensitive than the RAST (which is ablood test checking for specific IgE anti-bodies to each venom). Skin testing beginswith needle pricks to each individualspecies’ venom and if negative, it proceedsto sequential intradermal injections of thevenom at increasing doses. People withhypersensitivities to the venom from oneHymenoptera species may also have aller-gies to another. This is called cross-reac-tivity and is quite common within the sub-families Vespinae (aerial and ground-nest-ing yellow jackets, hornets, and bald-facedhornets) and Apidae (sweat bees, honeybees, and bumble bees) since their venomsare so similar. It is less common betweenbee, ‘vespid’, and paper wasp venoms, butmost people who have an allergic responseto the venom of one Hymenoptera speciesalso have an allergy to another.

Honey bee venom for testing andimmunotherapy is currently collected by theuse of an electrical micro-current grid thatstimulates bees to deposit their venom onthe underlying pad (with alarm pheromone

greatly magnifying the colony’s response).These bees do not die in the process ofstinging the grid. Vespid venom isobtained by individual venom sac dissec-tion. In the past, bee and vespid venomallergy desensitization was done withwhole body extracts. Whole body extractsfrom bees and vespids were not an effectivesource of venom immunotherapy like purevenom is today. (Fire) ant immunotherapyis still done with whole body extracts, how-ever, as different ant species do not crossreact with one another. Good, controlledeffectiveness studies have not been donefor fire ant whole body extracts as theyhave for pure venoms of the otherHymenoptera species.

Desensitization venom immunotherapy(allergy shots) entails the administration ofgradually larger doses of the venom(s) atregular intervals (usually twice a week) upto a target of 100 micrograms per dose overabout 6 months. Maintenance shots are thentypically continued (usually once a month)for at least 3 and usually 5 years. The deci-sion to discontinue immunotherapy is com-plex and treatment may be extended formany years in high risk patients (those withseveral reactions and/or increased exposure– such as beekeepers).

The goal of desensitization immunother-apy is simple. Repeated exposure to thevenom leads to a change in the way theregulatory T cells in the immune systemreact to the particular offending antigen.These T cells instruct the B cells to switchantibody production against venom pro-teins from allergic IgE to non-allergic IgG.

Figure 15. EpiPen Buddy Marterre, MD

Reaction Treatments

Normal Ice, Topical

Large LocalIce, +/- Anti-Histamine, +/-

Prednisone, +/- Singulair or Accolate

Systemic Allergy (Anaphylaxis)

Cutaneous

(Hives)

If over 16, Epinephrine

Desensitization Immunotherapy

Other Systems

(GI, Neuro)

Epinephrine, Benadryl, Prednisone,

Desensitization Immunotherapy

Cardiorespiratory

Epinephrine, Bronchodilators, Anti-

Histamines, Steroids,

Emergency Room/ Hospitalization,

Desensitization Immunotherapy

Massive Envenomation Emergency Room/ Hospitalization

Ocular Emergency Room/ Ophthalmologist

Table 6Insect Venom Reactions and Treatments

Marterre article Bee Stings part 2.qxp 7/14/2006 7:31 AM Page 3

IgG antibodies cannot cause mast cell acti-vation, and therefore mast cells do notdegranulate and there is no subsequentanaphylaxis. As more B cells produce IgGagainst bee venom proteins, the IgG willblock the antigen from being exposed tothe IgE-laden mast cells. There is even evi-dence of IgE anti-idiotypic IgG productionin patients undergoing desensitization (andbeekeepers receiving regular stings). Anti-Idiotypic antibodies are IgG antibodiesthat are directed at the hypervariableregion of the IgE antibody itself (an anti-body to an antibody or kind of like anoth-er key to ‘fool’ the IgE lock).

Venom allergy in the general populationand in beekeepers

In the general population, about 85 %people have a normal reaction to bee stings,with about 10 % having large local reac-tions, 4 % mild (cutaneous) systemic reac-tions, and 1 % severe anaphylaxis. Re-Stingreactions are typically similar in severity toearlier reactions. Certainly, beekeepers (andtheir family members and neighbors to alesser degree) have increased exposure tobee venom. About 25 % of beekeepers havehigh anti-bee venom IgE levels, and all bee-keepers have increased anti-bee venom IgG.Despite 25 % of beekeepers having highanti-bee venom IgE, anaphylaxis to beestings only occur in a minority of these indi-viduals, for unknown reasons. Beekeeper’sIgG levels increase and their IgE levels dropwith both the number of stings they receiveand their years of experience (thus regularstings have the same effect as allergy shotdesensitization). Because of their increasedexposure to bee venom, beekeepers havemore allergic responses to stings than thegeneral public. About 25 % of beekeepershave large locals and/or mild systemic(cutaneous) anaphylaxis to stings, and about3 % experience severe cardiorespiratoryanaphylaxis.

Skin testing is only indicated with a his-tory of systemic hives and/or a moresevere systemic reaction for patients over16. For those less than 16, systemic hivesalone is not an indication for skin testing.The history of the event and the reactionmust always be taken into account prior totesting. Also, many people with large localreactions to venomous stings, have IgEantibodies to venom proteins and wouldtherefore have a positive RAST and skintest. Because their risk of a subsequentsevere systemic reaction to re-sting isextremely low, individuals with a historyof large local reactions do not needimmunotherapy (and should not be testedin the first place). Also, neither skin pricktests nor RAST results correlate well withallergic responses in beekeepers.

One Italian study showed that beekeeperswith normal sting reactions incurred over100 stings per year whereas those with largelocals only incurred about 18. Another sur-vey found that 90 % of allergic beekeeperswore gloves as compared to 69 % of non-allergic beekeepers. Apparently, allergic

beekeepers take more precautions becauseof their heightened responses to stings.

Common allergic symptoms to inhaledallergens, such as pollen, insects andarthropods (like cockroaches and dustmites), animal dander, and fungi (molds)include runny nose, watery eyes, and anitchy face. People with these commonsymptoms are termed atopic. The risk of anallergic response to bee venom is higher inbeekeepers who are atopic, have a historyof a systemic reaction to a prior sting, andfewer years of beekeeping experience (lessthan 5 to 8 years). Atopic beekeepers canactually be allergic to beeswax, honey,propolis, and even bee parts.

In one very elegant study of 6 allergicbeekeepers, the skin within their largelocal reaction and their blood and urinewere analyzed 2 hours after a bee sting.Three of them had high histamine levelsand the other three had high leukotrienelevels, suggesting that allergic beekeeperseither have high histamine release orincreased leukotriene production, but notboth. This implies that about half of bee-keepers who have large local reactionsmight benefit from the immediate adminis-tration of a leukotriene inhibitor (Singulairor Accolate) (like me), whereas the otherhalf would benefit from anti-histamines(Benadryl, Allegra, Claritan, Zyrtec)before or very soon after the sting.

Desensitization results (general popula-tion) and beekeeper recommendations

Table 7, “Approximate Risk of (Re-)Sting Reaction Type” summarizes thisparagraph. It is data that I have pooled orcompiled from many different (reliable)sources, as no single study has been under-taken to define all these risks. Less than 1 - 2 % of people, who have experienced asevere systemic reaction to Hymenopteravenom, experience another severe systemicreaction to re-sting during immunotherapy.Venom immunotherapy or allergy shotsmarkedly reduce the risk of a systemicreaction to re-stings. After immunotherapyhas been undertaken for five years, the risk

of a systemic reaction is about 10 % (andonly 3.5 % severe cardiorespiratory) to are-sting. This is compared to a 50 – 60 %risk of re-experiencing a severe cardiores-piratory systemic reaction without anyimmunotherapy. If a systemic reactiondoes occur to a re-sting in someone despite100 microgram per month maintenancevenom immunotherapy, the dose is typical-ly increased to 200 micrograms. The risk ofsystemic reaction in people who have had alarge local reaction in the past is about 7 %,but none of those documented in large stud-ies have been severe responses.

Beekeepers with large local reactionswould be well advised to wear gloves.They may also consider a trial of takingeither a leukotriene inhibitor and/or ananti-histamine immediately after beingstung. They do not need to be evaluated ortreated with immunotherapy by an aller-gist. With time (5 – 8 years) and occasion-al repeated sting exposure (just like withallergy shots), large local reactions willprobably decrease in severity.

Anyone over 16 (beekeepers especially),who has experienced a generalized or sys-temic reaction (hives or anaphylaxis) tobee venom, should seek the advice of anallergist. Anaphylactic beekeepers who areinsistent on continuing to manage beesmight heed advice similar to that given byEich-Wanger and Muller:

1. Give up beekeeping (temporarily).2. Complete bee venom immunothera-

py (with a higher than usual mainte-nance dose of 200 micrograms ofvenom).

3. Return to beekeeping only after awell-tolerated sting challenge in theallergist’s office.

4. Always wear protective clothingwhile beekeeping and avoid morethan two stings at a time.

5. Keep one or two EpiPens availablewhen working hives or near beesand know how to use them.

6. Inform family members of your andyour bee yard’s whereabouts andcarry a cellular phone.

Table 7Approximate Risk of (Re-)Sting Reaction Type (Pooled Data)

Normal Large Mild - Mod SeverePopulation Reaction Local Anaphylaxis Anaphylaxis

General Public, NO VIT 85 % 10% 4 % 1 %

Beekeepers, NO VIT 70 % 20 % 7 % 3 %

History Large Local, NO VIT 7 % 0 %*

History Any Anaphylaxis, NO VIT 40 % 20 %

History Severe Anaphylaxis, NO VIT 20 % 55 %

History Any Anaphylaxis, 5 Years VIT 7 % 3.5 %

VIT = venom immunotherapy

* none reported

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Eich-Wanger and Muller reported on 69beekeepers with an allergic reaction to beestings, 42 of whom had had a severe reaction.Thirty-one of the 69 allergic beekeepers con-tinued beekeeping. Twenty-two of the 31,who continued beekeeping, received venomimmunotherapy and none of them developeda systemic reaction to re-stings, whereas 4 ofthe 9 who insisted on beekeeping withoutimmunotherapy did. Interestingly, the 22allergic beekeepers, who received allergyshots and successfully returned to beekeep-ing, then gave themselves one or two stingsper week during the active season and onesting per month during the winter (as contin-ued self-administered maintenance therapy).

About the authorI’ve had allergies all my life. I became

very interested in bees while I was in col-lege at Virginia Tech. But the beekeepingcourse I wanted to take interfered with bio-chemistry lab (my major), so instead I tookgraduate courses in immunology. Aftermedical school and a general surgery resi-dency, I did a fellowship in and then prac-ticed transplant surgery. So while I learnedand practiced more immunology (by trans-planting ‘foreign’ organs), my personalexperience with bee stings was still lack-ing. After my fellowship, I married anexperienced intensive care nurse, who isnow a certified pulmonary-allergy nurse.Then, I finally became a beekeeper and amnow a Master Beekeeper in NorthCarolina. I have large local reactions to beestings – and have experienced quite a fewof those! Being concerned about my risk ofmore serious reactions, I went back to theimmunology and allergy journals. Then,last year, I had an anaphylactic reaction(fortunately not to bee stings, but to salmon– which I had eaten many times before)!Thus, I am a doctor, a beekeeper, and apatient. In addition to all the photo credits,I’d also like to thank two excellent aller-gists for their review of this article: Aneysa

Sane, MD from Wake Forest UniversityMedical Center, and Larry Williams, MDfrom Duke University Medical Center.

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