marterre article bee stings 1.

qxp 6/14/2006 3:29 PM Page 1

Part I of Two Parts

by BUDDY MARTERRE, MD

Although its part of the business, few of us actually look forward to being stung. As
beekeepers we 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 those purposes and be informative to both the beginner beekeeper and the most expe-
rienced scientist. The first part will cover insects that sting, honey bee stings in particular, bee
venom biochemistry, precautions and sting prevention, the management of beekeeping
emergencies, and basic immunology and allergy. The second part will cover sting reaction
types and treatments, allergy testing and desensitization results, and specific recommenda-
tions for beekeepers.

Hymenoptera stings 1). Although solitary bees, such as sweat

T
he order Hymenoptera includes bees and carpenter bees, can inflict a
ants, bees, hornets, and wasps, sting, the risk of an allergic response to
many of which inflict stings (Table their venom is low because they are both
unaggressive and the amount of venom
they inject is low. More aggressive, prim-
itively social paper wasps, yellow jackets,
bald-faced hornets and European hornets
from the Family Vespidae (Figures 1 4)
as opposed to eusocial honey bee work-
ers from the Family Apidae can sting
more than once. If the flying stinging
insect that inflicts a sting is unidentified,
most often (unless the sting is still present

Figure 3. Bald Faced Hornet

(Dolichovespula maculata), courtesy of
Chris Wirth

Figure 1. Wasp (Polistes sp.), Buddy Figure 2. Yellow Jacket (Vespula vul-
Marterre, MD garis), courtesy of Jarmo Holopainen

Table 1
Hymenoptera Species with Venoms for Immunotherapy
Vespidae Wasps
Vespinae
Vespula ground-nesting yellow jackets
Dolichovespula aerial yellow jackets
Vespa hornets
Polistinae
Polistes paper wasps
Formicidae Ants
Myrmicinae
Solinopsis fire ants
Apidae Bees
Apinae
Apis honey bees Figure 4. European Hornet (Vespa
crabro), Buddy Marterre, MD
marterre article bee stings 1.qxp 6/14/2006 3:29 PM Page 2

pheromone. Guard bees are attracted to

dark colors, contrast (like hairlines), cer- Table 2
tain body odors (and perhaps the carbon Honey Bee Venom Biochemistry
dioxide you exhale), all drawing them Melittin *
toward your face and eyes. Certain per- Phospholipase A2
fumes, cosmetics, and banana oil may Apamin *
mimic alarm pheromone. Vibrations and Hyaluronidase
fast movements further aggravate the situ- Acid and Alkaline Phosphatases
ation. Mast Cell Degranulating Peptide *
Stinging bees flex their abdomens to Histamine, Dopamine, Norepinephrine
jab the sting into their target. The honey * unique to honey bees
bee sting (unlike the sting of other insects)
has a barb which leaves it attached to its
Figure 5. Imported Fire Ant (Solenopsis victim - complete with venom sac (Figure that facilitate biochemical reactions).
invicta), courtesy of Deyrup and Cover, 6). The sting apparatus is also covered by Together they cause the reaction that your
antweb.org muscles which continue to thrust the sting body has to the sting (pain, swelling, itch-
in the victim) the culprit was not a honey further into the victim. The venom then ing, redness, etc). Some of these chemi-
bee. Sting incidence in America varies travels down through the hollow, hypo- cals (or the bodys response to them) can
with region. Yellow jackets are more pop- dermic needle-type shaft (Figure 7). nine- also initiate very rapid reactions. An
ulous than honey bees in the north, wasps ty % of the venom sac empties in the first example would be the clotting cascade,
are more prevalent in the southwest, and 20 seconds. Alarm pheromone (highly which forms a clot within minutes of a
fire ants are more prevalent in the volatile isopentyl acetate and other alco- cut. Many of these proteins are also rec-
southeast. Imported fire ants - Family hols and esters) is released from the ognized as foreign by the human immune
Formicidae, genus Solenopsis - also have attached Koschevnikov gland, leaving the system (antigens) and lead to allergic
a sting apparatus (Figure 5). And their victim marked for further injury. In this reactions in some individuals.
venom is the most potent venom known in way, many old guards can be recruited in Forty fifty percent of honey bee
the animal kingdom! A general approxi- an exponential defensive response when venom is mellitin. Mellitin is a chemical
mation of flying insect sting incidence their hive is being threatened. And of that is unique to bee venom and is a
throughout the US is yellow jackets course, the primary perceived threat is cytolytic, which means that it directly
(Vespula and Dolichovespula) 50 %, you the beekeeper! bursts cells. It contributes to itching and
honey bee (Apis) 25 %, paper wasp Honey bee queens have more poorly swelling, and is the primary cause of the
(Polistes) 15 %, bumble bee (Bombus) 5 developed barbs than workers on their stings pain. Mellitin can also dilate blood
%, and European hornet (Vespa) 5 %. longer stings. The queen sting apparatus vessels, leading to low blood pressure.
has a stronger attachment to their ten twelve percent of honey bee venom
Honey bee stings abdomen and queens do not produce is Phospholipase A2 (the most potent
Bees sting defensively when their alarm pheromone. They reserve their allergen). Phospholipases are enzymes
hive, nest, or mound is thought to be stings for other queens, but have larger that help mellitin destroy cell membranes
under attack. For example, foraging bees venom sacs than workers, and can sting (cell membranes have lots of phospho-
will only sting if directly injured when multiple times. Worker bees die in the lipids in them). Apamin is also unique to
they are away from the hive. Mature, process of stinging, as their sting and bee venom (3 %) and is a neurotoxin it
adult, female worker bees in the hive sometimes other abdominal contents are is toxic to nerve conduction.
deploy the sting from its sheath in extruded. Hyaluronidase (2 %) is an enzyme that
response to alarm pheromone. This chem- breaks down hyaluronic acid, which is
ical messenger release is usually accom- Bee (and other insect) venom biochem- one of the components of connective tis-
panied by a short buzz and an astute bee- istry sue or the tissue in between your cells
keeper may even smell the banana oil-like Each European bee venom sac contains that hold you together (like little micro-
about 140 micrograms of venom (only scopic tendons). Hyaluronidase con-
about 100 micrograms per Africanized tributes to the spread of the reaction.
bee venom sac), but the average venom Phosphatases are enzymes that break off
delivered is a dose of about 50 micro- the phosphate portions of high-energy
grams. Needless to say, there are a lot of chemicals. Frequently these phosphate
very potent chemicals in bee venom that molecules begin cascades of other, very
are bad for you (Table 2). Many of these inflammatory biochemical reactions in
chemicals are peptides (small protein your body (like the clotting cascade).
chains) and enzymes (larger proteins Mast cell degranulating (MCD) peptides
do just what theyre named for they
cause the mast cells in your body to
release the many biochemicals (including
histamine) in their granules. Mast cells
will be covered more in the immunology
section later. Histamine causes leaky
capillaries and contributes to the familiar
wheal and flare reaction (slightly raised
red area that itches) in allergic or atopic
individuals.
Venoms from hornets (Vespa), aerial
yellow jackets (Dolichovespula), ground-
nesting yellow jackets (Vespula), and
paper wasps (Polistes) lack mellitin,
phospholipase A2, acid phosphatase,
Figure 6. Honey Bee Stinging an Arm, Figure 7. Sting Apparatus, courtesy of apamin, and MCD peptide. Their venom
courtesy of Zachary Huang, PhD Zachary Huang, PhD contains 10 - 25 % phospholipase A1 and
marterre article bee stings 1.qxp 6/14/2006 3:29 PM Page 3

B as well as antigen 5, which honey bee belong to the body (self), but distinguish
venom does not contain, however. The Table 4 these from proteins that dont belong (non-
proteins in the venoms of individual yel- Management of Emergencies self). The specialized white blood cells in
low jacket and hornet species (subfamily the immune system that do this are called
Vespinae) are quite similar. This leads to Close the hive if you can lymphocytes. Lymphocytes utilize com-
a lot of cross reactivity in the human Cover up plex protein receptors on their surface to
immune response to them. Thus, venoms Kill any bees inside your veil recognize self and non-self and they gener-
for testing hypersensitivity and Get your smoker ate two integrated responses to foreign
immunotherapy desensitization are typi- Walk at least 20 yards away into brush proteins (such as those from bee venom).
cally available separately for honey bees, (evergreens) One effector arm of the immune response
wasps, and mixed vespids. Return when calm (20 minutes) is the production of antibodies and the
other is the production of other controlling
Precautions and sting prevention away into some brush. Evergreens are par- and effector lymphocytes.
Good technique can reduce the number ticularly good at distracting bees. Walk. Do Antibodies are produced by B lympho-
of bee stings you receive (Table 3). not run (unless you can run a 5 minute mile)! cytes and are large complex proteins called
Realize that the mood of the hive can be Dont swat bees. Dont return to the scene of immunoglobulins (Ig). Immunoglobulins
affected by many things, such as season, the crime until you and the bees have calmed or antibodies have a hypervariable region
weather, and many factors that may only down (this takes about 10 or 20 minutes for that fits around a small piece of a foreign
be apparent to the bees. A long time ago I the bees I cant say for you)! protein (antigen) like a lock fits over a key.
gave up trying to predict the mood of the If a bee gets inside your veil, kill it The fit is even more specific than a key
five females I live with, much less the before it can sting your face. If you dont and lock, however, because it is in three
50,000 females in a bee hive! Therefore, have a veil on (heaven forbid) and bees are dimensions and also includes charge affin-
dont assume that a given hive will be flying into your face, close your eyes and ity (areas of negative charge on the antigen
gentle just because it had a good tempera- walk away (and get your veil). If you have line up with areas of positive charge in the
ment the last time you inspected it. Also, a bunch of bees inside your veil (more than cleft of the antibody). There are many dif-
if you are a suburban beekeeper (like me), two or three), take it off, cover your face ferent classes of antibodies, but the pri-
only keep very gentle bees near your and let them sting your hands. And remem- mary class in the bloodstream that is
house. And inquire as to your neighbors ber, every sting leaves you marked for involved with a normal immune response
possible venom allergies. more! is IgG and the class that is involved with
Work hives on warm, sunny, calm days. an allergic or hypersensitivity response is
Immunology and allergy IgE.
Table 3 The human immune system is highly The controlling cells of the immune
Precautions and Sting Prevention complex. Its basic function is to recognize response are called T lymphocytes. They
and destroy foreign tissue (like bacteria or recognize the foreign antigen with recep-
Wear white viral-infected cells). In order to do this, it tors on their surface (very much like anti-
and ALWAYS WEAR YOUR VEIL must not only recognize proteins that bodies) and can induce B cells to make
Avoid using perfumes and eating bananas
USE SMOKE judiciously
Work slowly and deliberately
Remove and smoke stings ASAP
Wash your bee suit and gloves frequently

Cold, windy conditions and impending

thunderstorms make for irritable bees.
Approach bee hives from the back. Do
not stand in their flight paths. Wear white
and ALWAYS WEAR YOUR VEIL.
Avoid using perfumes and eating bananas
before bee work. Use smoke judiciously,
but use it almost every time you work in
a hives brood nest (queen inspections
very soon after introduction and quick, Figure 8. Electron Micrographs of Mast Cells with Granules Left is scanning em,
gentle feeding operations are exceptions). Right is transmission em (showing granules), courtesy of Soman N Abraham, Duke
Work slowly and deliberately, avoiding University Medical Center
quick movements and hive vibrations.
Remove stings quickly without squeezing
them and smoke the stings as soon as pos-
sible. And wash your bee suit (and gloves
if you use them) frequently particularly
if youve received a bunch of stings!

Management of emergencies
Its better to be prepared for a major bat-
tle and not have one than to only prepare
for a minor skirmish and experience a
major war. What do you do if you drop or
knock over a hive and there are more
angry, stinging bees than you ever thought
possible coming at you? Table 4: Close the
hive if you can (easily). Cover up. Get
your smoker and smoke yourself (if its
still lit). Calmly walk at least 20 yards Figure 9. Diagram of Allergic Immune Response, by Rachel Alexandra Marterre
marterre article bee stings 1.qxp 6/14/2006 3:29 PM Page 4

specific antibodies to the antigen. Their and released by the mast cells are primari-
response may include recruiting other cells
Table 5 ly responsible for the late phase of anaphy-
Mast Cell Granule Contents and Products
to destroy it (using chemical messengers laxis. They attract other effector cells of
called cytokines similar to pheromones Histamine, Serotonin allergies, like eosinophils, basophils, and
in a bee hive) or by directly attacking the Enzymes (that destroy proteins or initiate neutrophils (which significantly contribute
foreign antigen themselves. In both the cascades) to allergic responses). Once these process-
case of antibody production by B cells and Heparin (anticoagulant) es get initiated, they can snow-ball in a
T lymphocyte generation, memory cells Eosinophil Chemotactic Factor of hurry and cause a lot of problems very
(both B and T) are generated that can then Anaphylaxis quickly. Again, if the allergic reaction
recognize the foreign antigen decades Neutrophil Chemotactic Factor becomes systemic (throughout the entire
later. This is how immunity to a virus or Leukotrienes body), it is called anaphylaxis.
bacteria or venomous sting can last a life- Prostaglandins Thats enough science for one article.
time, even though exposure to it may have Cytokines (which recruit other inflam- In part two, well discuss sting reaction
been years before or even in childhood. matory cells) types and treatments, allergy testing
The effector cells that are recruited by and desensitization results, and specific
the T cells and the antibody classes that B proteins or initiate other cascades), heparin recommendations for beekeepers.
cells make differ with different people, (an anticoagulant), and chemicals that
even in response to the same foreign anti- attract eosinophils (another allergic effec- About the author
gen. The cytokine messenger profiles (that tor cell) (Table 5). These primary media- Ive had allergies all my life. I became
recruit other effector cells) also differ from tors are released within minutes and their very interested in bees while I was in col-
individual to individual. Thus, some indi- effects on the human body begin very lege at Virginia Tech. But the beekeeping
viduals may make allergic IgE antibodies quickly. Histamine dilates blood vessels, course I wanted to take interfered with bio-
to bee venom antigens even though most makes them leaky, and activates the chemistry lab (my major), so instead I took
people make non-allergic IgG antibodies. endothelium (or lining of the capillaries). graduate courses in immunology. After
An allergic response to a venom antigen This leads to local edema (swelling), medical school and a general surgery resi-
(now called an allergen) is also quite com- warmth, redness, and the attraction of dency, I did a fellowship in and then prac-
plex. It begins with IgE antibodies and other inflammatory cells to the site. In ticed transplant surgery. So while I learned
mast cells. Mast cells are already present large amounts, it can drop blood pressure, and practiced more immunology (by trans-
in the sting site (Figure 8). Mast cell sur- and cause rapid swelling of the airway planting foreign organs), my personal
faces are loaded with IgE antibodies that (leading to stridor or an inability to experience with bee stings was still lack-
may react with many different types of breathe) and constrict bronchial tubes ing. After my fellowship, I married an
antigens or allergens. After venom is (causing an asthmatic attack). Histamine experienced intensive care nurse, who is
injected into the skin, at least two IgE anti- also irritates nerve endings (leading to now a certified pulmonary-allergy nurse.
bodies on the surface of a mast cell each itching or pain). Then, I finally became a beekeeper and am
react with the venom allergen, causing the Upon activation, mast cells also begin to now a Master Beekeeper in North
immediate release of preformed sub- synthesize secondary chemicals which Carolina. I have large local reactions to bee
stances in the granules of the mast cell, as have more delayed effects including stings and have experienced quite a few
well as the production of other new sub- prostaglandins, leukotrienes, and cy- of those! Being concerned about my risk of
stances. Refer to the Figure 9 for a basic tokines. Some of these secondary chemi- more serious reactions, I went back to the
diagram of an allergic immune response. cals (particularly the cytokines) are immunology and allergy journals. Then,
And recall, the mast cell degranulating responsible for the late phase of allergy, last year, I had an anaphylactic reaction
peptide in bee venom can cause this reac- which typically begins 2 4 hours after the (fortunately not to bee stings, but to
tion all by itself even without a typical insult. The prostaglandins and leukotrienes salmon which I had eaten many times
allergic response! With just a few stings, like histamine also cause bronchial before)! Thus, I am a doctor, a beekeeper,
mast cell degranulating peptides effects constriction, dilation of blood vessels and and a patient. In addition to all the photo
are only local, but with hundreds of stings leaky capillaries, but their onset is hours credits, Id also like to thank two excellent
the venom dose can cause toxic effects. later and their effects more long-lasting. allergists for their review of this article:
Once activated, mast cells release a lot Aspirin can actually exacerbate these Aneysa Sane, MD from Wake Forest
of very potent preformed chemicals from effects by causing more leukotrienes and University Medical Center, and Larry
their granules immediately, including his- fewer prostaglandins to be produced by the Williams, MD from Duke University
tamine, proteases (enzymes that destroy mast cells. The cytokines which are made Medical Center.
Marterre article Bee Stings part 2.qxp 7/13/2006 2:42 PM Page 1

Part II of Two Parts

by BUDDY MARTERRE, MD

Although its part of the business, few of us actually look forward to being stung. As beekeepers
we 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 those
purposes and be informative to both the beginner beekeeper and the most experienced. The first
part of this article covered insects that sting, honey bee stings in particular, basic bee venom
biochemistry, precautions and sting prevention, management of beekeeping emergencies, and
basic 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 gories: 1) venom removal or suction area (sometimes the entire extremity) than

T
he NORMAL reaction to a ven- devices, 2) bases such as urea, ammonia, a normal reaction (Figure 12). It starts as
omous insect sting is one of local and baking soda (to neutralize the acidity pain and a wheal (a several centimeter
pain and up to a few centimeters of of the venom), 3) hygroscopic agents (to swollen itch). A few hours after the sting
edema (swelling) that resolves in a few draw out the fluid) such as honey, mud, more redness, edema (swelling), and itch-
hours to a few days (Figure 10). Any sting and various pastes, and 4) lotions to ing develop. Over 12 48 hours, the area
can become secondarily infected, but for- decrease the itch such as calamine lotion, can become quite swollen, painful, and
tunately, this is fairly uncommon. Anusol, and Benadryl cream. All topical may also have some associated ecchymo-
Parenthetically, fire ant stings form a treatments require immediate application, sis (flecks of purple or red from a bruise
pseudopustule (Figure 11). These blisters so they are probably best used in non-bee- within the skin itself). The swelling gener-
may last for 10 days and should not be keeping situations. And as far as local ally begins to resolve after two days, but
confused with a true infection (pustule). applications for sting prevention is con- the site may remain tender (and continue to
The pseudopustules from fire ant stings cerned, DEET-containing bug sprays do itch) for a few more days. The total reac-
should be left intact (not unroofed or surgi- nothing to deter vespid stings. Normal tion lasts 4 7 days. Large locals around
cally drained). reactions are not an allergic response, and the face and mouth or on the hands may
The first treatment of a normal reac- allergy testing and desensitization are not cause temporary disability. The large local
tion is to quickly remove the sting and indicated after these. is IgE-mediated, and therefore is an aller-
smoke the area. Many local remedies have A LARGE LOCAL reaction is confined gic response.
been suggested for the treatment of bee to the general area of the sting, but over 24 Treatment of a large local includes ice
stings. These generally fall into 4 cate- 48 hours it develops into a much larger and elevation. Taking an anti-histamine or

Figure 11. Pseudopustules of Arm from

Fire Ant Stings Courtesy of Murray S
Figure 10. Normal Sting Reaction of Face Buddy Marterre, MD Blum
Marterre article Bee Stings part 2.qxp 7/13/2006 2:42 PM Page 2

bee stings should see an allergist for skin

testing and immunotherapy.
Anaphylaxis to insect venom accounts
for about 40 deaths per year in the US.
About 40 % (or about 16) of those are
attributable to honey bees, but this may be
an underestimate (due to some un-wit-
Figure 12. Large nessed venom-related deaths being falsely
Local Reaction of attributed to heart attacks). In comparison,
Hand and Wrist lightning strikes account for about 85, ani-
Buddy Marterre, MD mal bites 100, poisonings 3,600, smoking
over 150,000, and cancer almost 500,000
deaths per year in the US!
The treatment mainstay of anaphylaxis
is intramuscular epinephrine (Figure 15).
Dose depends on size. Children that weigh
less than 30 kilograms (66 pounds) need an
EpiPen Jr (0.15 mg) and larger children
a leukotriene-receptor antagonist very rhea, and abdominal cramps. Neurologic and adults need a regular EpiPen (0.30
soon after the sting may decrease the late symptoms include light-headedness, mg). In either case the injection is given
phase reaction. Personally, this is what I dizziness, and tremor, but light-headed- from the one-time-use pre-filled adminis-
do and it works for me! Oral steroids are ness and dizziness can also be due to a tration syringe into the anterolateral thigh
useful in treating large locals to stings drop in blood pressure, which would be a and may (and sometimes should) be
around the face and hands. Anti- cardiovascular effect. repeated every five minutes en route to an
Histamine choices are sedating drugs such Fortunately, cardiorespiratory system emergency room. There is also a new epi-
as diphenhydramine (Benadryl), and non- responses (severe ANAPHYLAXIS) occur nephrine injector called TwinJect, which
sedating ones, such as fexofenadine in less than 1 % of people incurring a bee can deliver two injections, but requires
(Allegra), loratidine (Claritin), and ceter- sting. Anaphylaxis may be preceded by partial disassembly between injections.
izine (Zyrtec). Benadryl and loratidine generalized itching, hives, and edema, and EpiPens and the TwinJect device require a
may be obtained without a prescription the specific cardiovascular and respiratory prescription as there may be some risk to
(over the counter). Caution is advised with system reactions can progress fairly rapid- administering epinephrine to someone
driving (or continued beekeeping) after ly (over 1 to 30 minutes). They include with severe heart disease. EpiPens come
taking a sedating anti-histamine (particu- wheezing, stridor (airway compromise and with practice administration syringes and
larly if high doses are taken), however. inability to breathe), shock (very low instructions. If you, anyone in your family,
Oral steroids in the form of prednisone blood pressure causing collapse), loss of or the neighbors to your bee yard have a
short courses and dose packs require eval- consciousness, and death. Beekeepers, systemic allergy, have at least one epineph-
uation by a physician and prescription. As family members (or anyone) who has had rine injector on hand and know how to use
mentioned above, another class of pre- a moderate or severe systemic allergy to it! Other treatments for anaphylaxis
scription drugs that may help are the include bronchodilator inhalers (prescrip-
leukotriene-receptor antagonists mon- tion), and anti-histamines and steroids - as
telukast (Singulair) and zafirlukast for large local reactions. Anyone experi-
(Accolate). These drugs block the encing anaphylaxis (epinephrine-treated or
leukotriene receptors on mast cells and not) needs to be transported directly to an
eosinophils and both have peak activity 3 emergency room. Most of these patients
4 hours after taking them. People who will be admitted to the hospital overnight
have (only) had a large local response, as sometimes the reactions recur (typically
have little or no risk of a severe, life- at 4 6 hours). Remember those secondary
threatening anaphylactic response in the chemicals that the mast cells make that
future. Therefore, even though a large cause the late phase of allergy? Allergy
local reaction is an allergic response, testing and venom immunotherapy desen-
allergy testing and desensitization are not sitization is indicated for anyone with a
indicated after these. Figure 13. Urticaria or Hives systemic allergic response to insect stings,
SYSTEMIC ALLERGIC responses courtesy of Dr. Raymond J. Mullins, including diffuse hives in anyone over 16
involve two or more organ systems of allergycapital.com.au years of age. Allergy testing is not recom-
the body and are called ANAPHYLAX-
IS. They can be mild and manifest as
purely cutaneous (skin) responses, or
may include symptoms of the gastroin-
testinal system or nervous system, or
worse, the cardiorespiratory systems. A
systemic cutaneous (or skin) response
must be distant from the sting site (to
differentiate it from a large local reac-
tion) and typically involves the trunk or
scalp. Generalized cutaneous responses
include urticaria or hives (the familiar,
itchy 5 40 millimeter red wheals and
slightly raised flares Figure 13) and/or
angioedema (a rapidly-developing mas-
sive swelling of the face Figure 14).
Gastrointestinal symptoms include a Figure 14. Facial Angioedema Same patient, before and after treatment
metallic taste, nausea, vomiting, diar- courtesy of siamhealth.com
Marterre article Bee Stings part 2.qxp 7/14/2006 7:31 AM Page 3

greatly magnifying the colonys response).

These bees do not die in the process of
stinging the grid. Vespid venom is
obtained by individual venom sac dissec-
tion. In the past, bee and vespid venom
allergy desensitization was done with
whole body extracts. Whole body extracts
from bees and vespids were not an effective
Figure 15. EpiPen Buddy Marterre, MD source of venom immunotherapy like pure
venom is today. (Fire) ant immunotherapy
mended for urticaria / hives alone in a the risk of a systemic reaction with re-sting is still done with whole body extracts, how-
child (under 16). is 20 % or greater and has also had a posi- ever, as different ant species do not cross
MASSIVE ENVENOMATION (some- tive skin test to the venom. Skin testing is react with one another. Good, controlled
times called a toxic reaction) occurs with more sensitive than the RAST (which is a effectiveness studies have not been done
greater than 500 honey bee stings. This is blood test checking for specific IgE anti- for fire ant whole body extracts as they
not an allergic response, but is related to bodies to each venom). Skin testing begins have for pure venoms of the other
the large amount of venom received by the with needle pricks to each individual Hymenoptera species.
victim. Very young children or chronically species venom and if negative, it proceeds Desensitization venom immunotherapy
ill elderly people may be poisoned by 150 to sequential intradermal injections of the (allergy shots) entails the administration of
(or more) stings. The dose of bee stings venom at increasing doses. People with gradually larger doses of the venom(s) at
that has been calculated to kill half of the hypersensitivities to the venom from one regular intervals (usually twice a week) up
victims (LD50) is 19 stings per kilogram Hymenoptera species may also have aller- to a target of 100 micrograms per dose over
of body weight. Initial symptoms of bee gies to another. This is called cross-reac- about 6 months. Maintenance shots are then
venom toxicity include generalized edema tivity and is quite common within the sub- typically continued (usually once a month)
(swelling), fatigue, nausea, vomiting, families Vespinae (aerial and ground-nest- for at least 3 and usually 5 years. The deci-
fever, and unconsciousness. The reaction is ing yellow jackets, hornets, and bald-faced sion to discontinue immunotherapy is com-
sometimes delayed by as much as 6 days hornets) and Apidae (sweat bees, honey plex and treatment may be extended for
and therefore requires immediate trans- bees, and bumble bees) since their venoms many years in high risk patients (those with
portation to an emergency room and hospi- are so similar. It is less common between several reactions and/or increased exposure
talization. The problems are primarily the bee, vespid, and paper wasp venoms, but such as beekeepers).
result of rhabdomyolysis (breakdown of most people who have an allergic response The goal of desensitization immunother-
muscle tissue) and myoglobinuria (the to the venom of one Hymenoptera species apy is simple. Repeated exposure to the
muscle breakdown products in the blood also have an allergy to another. venom leads to a change in the way the
leading to kidney failure). Hemolysis Honey bee venom for testing and regulatory T cells in the immune system
(burst red blood cells), DIC or disseminat- immunotherapy is currently collected by the react to the particular offending antigen.
ed intravascular coagulation (abnormal use of an electrical micro-current grid that These T cells instruct the B cells to switch
clot formation inside the blood vessels stimulates bees to deposit their venom on antibody production against venom pro-
with an overuse of clotting factors and sub- the underlying pad (with alarm pheromone teins from allergic IgE to non-allergic IgG.
sequent bleeding) can also occur. Kidney
failure and cardiac arrest cause most toxic Table 6
bee sting deaths (which are considerably Insect Venom Reactions and Treatments
rarer than anaphylaxis deaths).
OCULAR (or eyeball) STINGS are for- Reaction Treatments
tunately quite rare (because of the
extremely fast human blink response), but Normal Ice, Topical
when they do occur they frequently lead to
blindness. Immediate attention by an oph-
thalmologist is warranted. Specific ocular Ice, +/- Anti-Histamine, +/-
sting injuries include corneal edema, Large Local
Prednisone, +/- Singulair or Accolate
hyphema (blood in the anterior chamber of
the eye), lens dislocation, cataract, and
optic neuritis (inflammation of the optic Systemic Allergy (Anaphylaxis)
nerve). Prevention is clearly the key to
these injuries. Veils only cost a few dollars Cutaneous If over 16, Epinephrine
and can be donned in seconds! Table 6 (Hives) Desensitization Immunotherapy
summarizes venom reaction types and
treatment.
Other Systems Epinephrine, Benadryl, Prednisone,
Allergy testing and desensitization
(GI, Neuro) Desensitization Immunotherapy
Although large local reactions are aller-
gic responses, allergy testing and desensi-
tization immunotherapy are not indicated Epinephrine, Bronchodilators, Anti-
after these because the risk of a severe sys-
temic reaction to re-sting is extremely low.
Histamines, Steroids,
Cardiorespiratory
People who have experienced a systemic Emergency Room/ Hospitalization,
allergic response (including urticaria or Desensitization Immunotherapy
diffuse hives in someone over 16) certain-
ly benefit from allergy testing and subse-
quent desensitization immunotherapy. Massive Envenomation Emergency Room/ Hospitalization
Desensitization venom immunotherapy
(allergy shots) is warranted in anyone who Ocular Emergency Room/ Ophthalmologist
has had a systemic reaction and in whom
Marterre article Bee Stings part 2.qxp 7/13/2006 2:42 PM Page 4

IgG antibodies cannot cause mast cell acti-

vation, and therefore mast cells do not Table 7
degranulate and there is no subsequent Approximate Risk of (Re-)Sting Reaction Type (Pooled Data)
anaphylaxis. As more B cells produce IgG
against bee venom proteins, the IgG will Normal Large Mild - Mod Severe
block the antigen from being exposed to Population Reaction Local Anaphylaxis Anaphylaxis
the IgE-laden mast cells. There is even evi-
dence of IgE anti-idiotypic IgG production General Public, NO VIT 85 % 10% 4% 1%
in patients undergoing desensitization (and
beekeepers receiving regular stings). Anti- Beekeepers, NO VIT 70 % 20 % 7% 3%
Idiotypic antibodies are IgG antibodies
that are directed at the hypervariable History Large Local, NO VIT 7% 0 %*
region of the IgE antibody itself (an anti-
body to an antibody or kind of like anoth- History Any Anaphylaxis, NO VIT 40 % 20 %
er key to fool the IgE lock).
History Severe Anaphylaxis, NO VIT 20 % 55 %
Venom allergy in the general population
and in beekeepers History Any Anaphylaxis, 5 Years VIT 7% 3.5 %
In the general population, about 85 %
people have a normal reaction to bee stings, VIT = venom immunotherapy
with about 10 % having large local reac- * none reported
tions, 4 % mild (cutaneous) systemic reac-
tions, and 1 % severe anaphylaxis. Re-Sting beekeepers take more precautions because of a systemic reaction is about 10 % (and
reactions are typically similar in severity to of their heightened responses to stings. only 3.5 % severe cardiorespiratory) to a
earlier reactions. Certainly, beekeepers (and Common allergic symptoms to inhaled re-sting. This is compared to a 50 60 %
their family members and neighbors to a allergens, such as pollen, insects and risk of re-experiencing a severe cardiores-
lesser degree) have increased exposure to arthropods (like cockroaches and dust piratory systemic reaction without any
bee venom. About 25 % of beekeepers have mites), animal dander, and fungi (molds) immunotherapy. If a systemic reaction
high anti-bee venom IgE levels, and all bee- include runny nose, watery eyes, and an does occur to a re-sting in someone despite
keepers have increased anti-bee venom IgG. itchy face. People with these common 100 microgram per month maintenance
Despite 25 % of beekeepers having high symptoms are termed atopic. The risk of an venom immunotherapy, the dose is typical-
anti-bee venom IgE, anaphylaxis to bee allergic response to bee venom is higher in ly increased to 200 micrograms. The risk of
stings only occur in a minority of these indi- beekeepers who are atopic, have a history systemic reaction in people who have had a
viduals, for unknown reasons. Beekeepers of a systemic reaction to a prior sting, and large local reaction in the past is about 7 %,
IgG levels increase and their IgE levels drop fewer years of beekeeping experience (less but none of those documented in large stud-
with both the number of stings they receive than 5 to 8 years). Atopic beekeepers can ies have been severe responses.
and their years of experience (thus regular actually be allergic to beeswax, honey, Beekeepers with large local reactions
stings have the same effect as allergy shot propolis, and even bee parts. would be well advised to wear gloves.
desensitization). Because of their increased In one very elegant study of 6 allergic They may also consider a trial of taking
exposure to bee venom, beekeepers have beekeepers, the skin within their large either a leukotriene inhibitor and/or an
more allergic responses to stings than the local reaction and their blood and urine anti-histamine immediately after being
general public. About 25 % of beekeepers were analyzed 2 hours after a bee sting. stung. They do not need to be evaluated or
have large locals and/or mild systemic Three of them had high histamine levels treated with immunotherapy by an aller-
(cutaneous) anaphylaxis to stings, and about and the other three had high leukotriene gist. With time (5 8 years) and occasion-
3 % experience severe cardiorespiratory levels, suggesting that allergic beekeepers al repeated sting exposure (just like with
anaphylaxis. either have high histamine release or allergy shots), large local reactions will
Skin testing is only indicated with a his- increased leukotriene production, but not probably decrease in severity.
tory of systemic hives and/or a more both. This implies that about half of bee- Anyone over 16 (beekeepers especially),
severe systemic reaction for patients over keepers who have large local reactions who has experienced a generalized or sys-
16. For those less than 16, systemic hives might benefit from the immediate adminis- temic reaction (hives or anaphylaxis) to
alone is not an indication for skin testing. tration of a leukotriene inhibitor (Singulair bee venom, should seek the advice of an
The history of the event and the reaction or Accolate) (like me), whereas the other allergist. Anaphylactic beekeepers who are
must always be taken into account prior to half would benefit from anti-histamines insistent on continuing to manage bees
testing. Also, many people with large local (Benadryl, Allegra, Claritan, Zyrtec) might heed advice similar to that given by
reactions to venomous stings, have IgE before or very soon after the sting. Eich-Wanger and Muller:
antibodies to venom proteins and would 1. Give up beekeeping (temporarily).
therefore have a positive RAST and skin Desensitization results (general popula- 2. Complete bee venom immunothera-
test. Because their risk of a subsequent tion) and beekeeper recommendations py (with a higher than usual mainte-
severe systemic reaction to re-sting is Table 7, Approximate Risk of (Re-) nance dose of 200 micrograms of
extremely low, individuals with a history Sting Reaction Type summarizes this venom).
of large local reactions do not need paragraph. It is data that I have pooled or 3. Return to beekeeping only after a
immunotherapy (and should not be tested compiled from many different (reliable) well-tolerated sting challenge in the
in the first place). Also, neither skin prick sources, as no single study has been under- allergists office.
tests nor RAST results correlate well with taken to define all these risks. Less than 4. Always wear protective clothing
allergic responses in beekeepers. 1 - 2 % of people, who have experienced a while beekeeping and avoid more
One Italian study showed that beekeepers severe systemic reaction to Hymenoptera than two stings at a time.
with normal sting reactions incurred over venom, experience another severe systemic 5. Keep one or two EpiPens available
100 stings per year whereas those with large reaction to re-sting during immunotherapy. when working hives or near bees
locals only incurred about 18. Another sur- Venom immunotherapy or allergy shots and know how to use them.
vey found that 90 % of allergic beekeepers markedly reduce the risk of a systemic 6. Inform family members of your and
wore gloves as compared to 69 % of non- reaction to re-stings. After immunotherapy your bee yards whereabouts and
allergic beekeepers. Apparently, allergic has been undertaken for five years, the risk carry a cellular phone.
Marterre article Bee Stings part 2.qxp 7/13/2006 2:42 PM Page 5

Eich-Wanger and Muller reported on 69 Sane, MD from Wake Forest University gy to insect stings in children, with and
beekeepers with an allergic reaction to bee Medical Center, and Larry Williams, MD without venom immunotherapy. The
stings, 42 of whom had had a severe reaction. from Duke University Medical Center. New England Journal of Medicine.
Thirty-one of the 69 allergic beekeepers con- 351(7):668-674.
tinued beekeeping. Twenty-two of the 31, Selected Bibliography Golden DBK, Kwiterovich KA, Kagey-
who continued beekeeping, received venom Annila IT, Annila PA, and P Morsky. Sobotka A, Valentine MD, and LM
immunotherapy and none of them developed 1997. Risk assessment in determining Lichtenstein. 1996. Discontinuing
a systemic reaction to re-stings, whereas 4 of systemic reactivity to honeybee stings in venom immunotherapy: Outcome after
the 9 who insisted on beekeeping without beekeepers. Annals of Allergy, Asthma, five years. Journal of Allergy and
immunotherapy did. Interestingly, the 22 and Immunology. 78(5):473-477. Clinical Immunology. 97(2):579-587.
allergic beekeepers, who received allergy Annila IT, Karjalainen ES, Annila PA, Goodman L. 2003. Form and Function in
shots and successfully returned to beekeep- and PA Kuusisto. 1996. Bee and wasp the Honey Bee. International Bee
ing, then gave themselves one or two stings sting reactions in current beekeepers. Research Association, Cardiff, UK.
per week during the active season and one Annals of Allergy, Asthma, and Lerch E, and UR Muller. 1998. Long-
sting per month during the winter (as contin- Immunology. 77(5):423-427. Term protection after stopping venom
ued self-administered maintenance therapy). Annila I, Saarinen JV, Nieminen MM, immunotherapy: Results of re-stings in
Moilanen E, Hahtola P, and IT 200 patients. Journal of Allergy and
About the author Harvim. 2000. Bee venom induces high Clinical Immunology. 101(5):606-612.
Ive had allergies all my life. I became histamine or high leukotriene C4 release Levine MI, Lockey RF, eds. 2003.
very interested in bees while I was in col- in skin of sensitized beekeepers. Journal Monograph on Insect Allergy, 4th ed,
lege at Virginia Tech. But the beekeeping of Investigational Allergology and American Academy of Asthma, Allergy
course I wanted to take interfered with bio- Clinical Immunology. 10(4):223-228. and Immunology, Pittsburgh, PA: David
chemistry lab (my major), so instead I took Arcieri ES, Franca ET, de Oliveria HB, Lambert Associates.
graduate courses in immunology. After De Abreu Ferreira L, Ferreira MA, Reisman RE. 1992. Natural history of
medical school and a general surgery resi- and FJ Rocha. 2002. Ocular lesions insect sting allergy: Relation to severity
dency, I did a fellowship in and then prac- arising after stings by hymenopteran of symptoms of initial sting anaphylaxis
ticed transplant surgery. So while I learned insects. Cornea. 21(3):238-330. to re-sting reactions. Journal of Allergy
and practiced more immunology (by trans- Bousquet J, Menardo J-L, Aznar R, and Clinical Immunology. 90(3 Pt
planting foreign organs), my personal Robinet-Levy M, and F-B Michel. 1):335-339.
experience with bee stings was still lack- 1984. Clinical and immunologic survey Schmidt, JO. 1992. Allergy to Venomous
ing. After my fellowship, I married an in beekeepers in relation to their sensiti- Insects. In The Hive and the Honey Bee.
experienced intensive care nurse, who is zation. Journal of Allergy and Clinical JM Graham, ed. Dadant & Sons,
now a certified pulmonary-allergy nurse. Immunology. 73(3):332-340. Hamilton, IL, pp.1209-1269.
Then, I finally became a beekeeper and am Davis CF. 2004. The Honey Bee Inside van Halteren HK, van der Linden P-
now a Master Beekeeper in North Out. Bee Craft Limited, Stoneleigh, UK. WG, Burgers SA, and AKM
Carolina. I have large local reactions to bee Eich-Wanger C, and UR Muller. 1998. Bartelink. 1996. Hymenoptera sting
stings and have experienced quite a few Bee sting allergy in beekeepers. Clinical challenge of 348 patients: Relation to
of those! Being concerned about my risk of and Experimental Allergy. 28(10):1292- subsequent field stings. Journal of
more serious reactions, I went back to the 1298. Allergy and Clinical Immunology.
immunology and allergy journals. Then, Golden DBK, Kagey-Sobotka A, and LM 97(5):1058-1063.
last year, I had an anaphylactic reaction Lichtenstein. 2000. Survey of patients Vetter RS, Visscher PK, and S
(fortunately not to bee stings, but to salmon after discontinuing venom immunothera- Camazine. 1999. Mass envenomations
which I had eaten many times before)! py. Journal of Allergy and Clinical by honey bees and wasps. Western
Thus, I am a doctor, a beekeeper, and a Immunology. 105(2 Pt 1):385-390. Journal of Medicine. 170(4):223-227.
patient. In addition to all the photo credits, Golden DBK, Kagey-Sobotka A, Winston ML. 1987. The Biology of the
Id also like to thank two excellent aller- Norman PS, Hamilton RG, and LM Honey Bee. Harvard University Press,
gists for their review of this article: Aneysa Lichtenstein. 2004. Outcomes of aller- Cambridge, MA.