24 Februarie 1979 SA MEDIESE TYDSKRIF 285
Desensitization of Patients with Bee Sting Allergy Using
Pure Bee Venom
C. ABKIEWICZ, R. LOMNITZER, A. R. RABSON
SUMMARY SUBJECTS AND METHODS
Forty patients who had previously experienced severe sys- Patients
temic reactions after a bee sting were desensitized using
pure bee venom. A modified 'Rush' regimen was employed
Forty patients took part in the trial. They ranged in
whereby patients received two injections a week and
age from 5 to 40 years (mean age -14,1 years) and in-
reached maximal desensitization in 5 weeks. Eleven patients
cluded 22 males and 18 females. All patients had a
history of severe systemic reactions which required medi-
have subsequently been stung again and have developed
cal attention after bee stings. These reactions included
no generalized reaction. Although this form of desensitiza-
generalized urticaria, urticaria at a site distant from the
tion is considered to be highly effective in protecting sen-
sitive patients, both generalized and local side-effects were
bee sting, laryngeal oedema, bronchospasm or anaphylaxis.
frequent. Maintenance desensitizing injections are required
Patients with swelling or oedema only at the site of the
every month for an indefinite period. It is concluded that
sting, even when this swelling involved an entire limb,
desensitization with pure bee venom should be undertaken
were not included in this study.
only in highly selected sensitive patients, and should be
On the first visit all patients were skin tested with pure
bee venom according to the technique of Hunt et af.· Pre-
performed under strict control.
liminary skin prick tests were performed using 0,1 p.g/ml
of venom and if this was negative 1,0 fLg/ml was em-
S. Air. med. J., 55, 285 (1979). ployed. Thereafter direct skin testing was performed by
an intradermal injection of 0,05 ml of the two test solu-
The occurrence of serious reactions to the sting of the tions. Skin reactions were evaluated at 15 minutes and a
h~ney bee (Apis melli/era) is not uncommon, and bees are
positive skin test was defined as a wheal 5 - 10 mm in
saId to be responsible for more deaths each year than diameter associated with erythema 10 - 20 mm in diameter.
all other poisonous animals.' This problem exists to a
greater extent in southern Africa where bee populations Protocol for Desensitization
t~nd to be ~ore volatile and will attack anything which
Pure bee venom diluted in normal saline containing
dIsturbs thelf nests." This situation urgently necessitates
0,03 mg/loo ml human serum albumin was prepared at
adequ~te protection against the effects of bee stings.
the South African Institute for Medical Research. A
UntIl recently all patients allergic to bee venom have modified 'Rush' treatment regimen was used in which
been treated with multiple injections of crushed whole patients are treated each week until a maintenance dose
insect bodies. Although such treatment has been described of 100 p.g of venom is reached. On the first visit 1,0
as ~ighly :ffective in protecting victims against anaphy-
JLg of venom was injected subcutaneously into the forearm.
lactic reactIOns,'" a more recent report questions its value:
If no untoward reaction was observed after a period of
~urthermore, therapy with whole-body extract fails to
20 minutes, a IQ-fold higher dose (ID p.g) was injected. A
mcrease IgG antibody levels against venom proteins, a
week later the patients were again given 10 p.g and then
response thought to be essential for protection in insect
a further injection containing 30 p.g. During the following
allerg.y: and may in fact sensitize patients to insect body
weeks they received 30 p.g and 50 JJ.g, 50 JJ.g and 75 fJ-g, and
protem and produce a syndrome resembling serum
75 Jig and 100 rfLg. The following week the patients received
only one injection of 100 Jig and the time interval of
Recently the use of pure bee venom has been advocated
therapy was increased at this stage, 100 ,p.g being given
for both direct skin testing· and treatment' of patients
2 weeks after the last injection, 3 weeks later and finally
who are hypersensitive to bee venom. This study describes
4 weeks later. Maintenance injections (IOO p.g) were then
our experience with the desensitization of 40 carefully
given at monthly intervals.
selected highly allergic patients with pure bee venom.
Dep~ent o~ Immunology, School of Pathology, South Skin Tests
African Institute for Medical Research and University of
the Witwatersrand, Johannesburg Of the 40 patients, 36 developed a positive skin re-
C. ABKIEWICZ, M.B. B.CH., F.C.P. (S.A.) sponse to an intradermal injection of 0,05 ml of the
R. LOMNITZER, PH.D. solution containing 1 rfLg venom per millilitre. One patient
A. R. RABSON, M.B. B.CH., D. PATH., D.C.P. developed a response after a scratch test using the same
Date. received: 29 September 1978. concentration of venom. Three patients who had been
Reprmt requests to: Professor A. R. Rabson, PO Box 1038, Johannesburg
2000. RSA. stung during the previous 4 days had negative responses
286 SA MEDICAL JOURNAL 24 February 1979
to both scratch and intradermal tests. In all 3 cases there sixth maintenance dose she developed bronchospasm and
was no doubt that the offending sting had been caused by urticaria which were reversed with adrenaline, and since
a bee. that time she has continued to receive 100 ,p.g of venom
montWy without further reaction.
Patients have now been followed up for a period ranging DISCUSSION
from 8 to 14 months. Of the 40 patients, 11 have had These studies indicate the value of pure venom immuno-
subsequent bee stings. All were receiving maintenance therapy in the treatment of patients who are hypersensi-
injections and whereas before immunotherapy they de- tive to bee venom. Of the 40 patients desensitized with
monstrated severe, in some cases life-threatening, systemic pure venom, 11 have subsequently been restung. In
reactions, only mild local reactions resulted from the sting all of these patients only limited local reactions were ob-
after the course of therapy. served in contrast to serious life-threatening episodes ex-
perienced before immunotherapy. These results support the
Local Side-Effects observations of Hunt et al." who showed that after treat-
Virtually all patients demonstrated some degree of local ment with pure venom 58 patients with insect hypersen-
reaction after desensitization injections. Local wheals ap- sitivity could be challenged by a sting without any adverse
reaction. Similar results were obtained by other workers"tO
peared within 10 minutes of injection but settled within
60 minutes. Late local reactions, however, were extremely who indicated that individual patients who developed ana-
common and appeared 1 or 2 days after injection as large phylaxis after insect stings could be desensitized with pure
indurated areas often involving the entire limb and lasting venom, and would subsequently tolerate a controlled sting
for 24 - 72 hours. Reactions were worse at the beginning without developing a reaction. It has also been shown that
of the course and tended to diminish in severity as de- continued venom administration produces a rise in IgG-
sensitization proceeded. Six patients who had not been specific antibodies, the presence of which correlates with
excessively troubled by local reactions developed severe protection from subsequent stings in persons who pre-
early or late local responses while on maintenance therapy viously have had anaphylactic reactions." Passively ad-
necessitating injections (lOO ,p-g) at more frequent inter- ministered IgG antibody has provided protection in a
vals. group of known sensitive individuals:'
Although there appears to be little doubt about the
efficiency of pure venom desensitization in protecting
patients against subsequent anaphylactic episodes, the
Five of the 40 patients experienced some systemic re- frequency of side-effects noted in this study may severely
action during the course of immunotherapy or while hamper the unrestricted use of this form of therapy in the
receiving maintenance injections. All reactions were easily general population. Five patients (12,5%) experienced
reversible with subcutaneous adrenaline or intravenous some manifestations of generalized anaphylaxis. In 4 of
mepyramine maleate. Two children aged 8 and 11 re- them symptoms appeared during desensitization, whereas
spectively developed bronchospasm and urticaria after in the remaining patient an adverse reaction developed
their third visits and the desensitization protocol was al- on one occasion only, 10 minutes after a routine monthly
tered so that each child received only one injection a week maintenance injection. It is difficult to explain this un-
containing 10 ,p.g more venom than was tolerated on the expected severe reaction which could have been due to
previous visit. In this manner both patients reached the rapid absorption of venom perhaps as a result of in-
maintenance dose of 100 ,p.g without further trouble. advertent injection into a venule or capillary. All
A 14-year-old girl developed a severe generalized re- generalized reactions started initially with itching of the
action from the commencement of immunotherapy. She palate followed by some bronchospasm with or without
continued to react even when the venom dose was diluted urticaria, and were easily reversed with subcutaneous
one thousand times, and developed the same reaction adrenaline.
when diluent free of venom was employed. It was there- Local reactions at the site of injection were present in
fore decided to continue desensitization even though re- most patients but tended to lessen in severity as desensi-
actions were occurring and the strength of injections was tization progressed. These reactions were most severe the
gradually increased, the patient being given adrenaline day after the injection and swelling usually disappeared 2
when severe reactions developed. She is at present receiving or 3 days later. A number of patients who experienced
monthly maintenance injections although she still develops only minimal local reactions during the desensitization pro-
some bronchospasm and urticaria. gramme developed sudden unexpectedly severe reactions
A 7-year-old boy was desensitized without complications during maintenance therapy. In these patients further in-
but developed a severe anaphylactic reaction after his jections were given at shorter intervals, usually every 2 or 3
fifth maintenance injection. This was reversed and the weeks until local reactions were no longer obtained, after
patient .continues to receive monthly boosters without which maintenance injections were again given every 4
further problems. weeks. We are unable to explain the unpredictable nature
An adult woman developed signs of anaphylaxis on her of these local reactions. The desensitizing material con-
third and fifth visits but was successfully desensitized tained 0,03 mg/lOO ml human serum albumin, which is
and receives maintenance injections monthly. After the sufficient to prevent nonspecific loss of activity of venom
24 Februarie 1979 SA MEDIESE TYDSKRIF 287
;iue eIther to its binding to glass or to denaturation. Further- therefore, confirm the efficacy and safety of pure venom
more, vials containing venom were well shaken before use testing and desensitization for the prevention of life-
~o that fluctuations in the venom dose were unlikely. threatening allergic reactions to bee stings.
Although this report confirms the usefulness of pure
pee venom immunotherapy in protecting patients with We wish to acknowledge the advice and assistance of Dr
jmown anaphylactic reactions to bee stings, a number of Anne K. Sobotka of the lohns Hopkins University School
of Medicine, Baltimore, USA.
problems still exist. Systemic and local reactions are de-
I:idedly more common than those experienced during the
llsual desensitization programmes in which respiratory al- REFERENCES
lergens are used, and greater care and vigilance will be I. Miche~er. C. D. (1974): The Social Behaviour 0/ the Bees. Cambridge,
M1SS.: H:lrvard U:liversity Press.
required of the physician. Furthermore, the optimal regi- 2. Crewe, R. M. (1976): S. Afr. J. Sci., 72. 209.
men has not yet been established but it appears that month- 3. Ordm,n, D. (1965): Int. Arch. Allergy, 28. 366.
4. M~eller, H. L. (1971): Pediatrics, 59, 713.
lY maintenance injections will be required for an unlimited 5. Hunt. K. J., Vale'tine. M. D., Sobotka, A. K. et al. (1978): ew
period. These drawbacks make an accurate diagnosis essen- Engl. J. Med., 299, 157.
6. Light, W. C., Reisman, R. E., Shimizu, M. et al. (1977): J. Allergy
~ial in each case and patients should be carefully evaluated clin. Imm'lnol., 59, 247.
7. Hunt, K. J., Sobotk., A. K., Valentine, M. D. et al. (1978): Ibid.,
before a decision is made to desensitize. Hypersensitivity 61, 48.
8. HlI~t, K. J., Valentine. M. D., Sobotb. A. K. et al. (1976): Ann.
i:an be easily confirmed by using pure bee venom for skin intern. Med., 85, 56.
resting. Patients should, however, wait for 2 - 3 weeks after 9. Lich'enstein, L. M., Valentine, M. D. and Sobotka, A. K. (1974):
N. Engl. J. Med., 290. 1223.
:l sting before confirmatory testing is performed, as those 10. Valentine, M. D., Hunt, K. J. Sobotka, A. K. et al. (1976): J.
patients tested soon after a sting had negative skin re- Allergy clin. Immllnol., 57, 247.
11. B~sse, W. W., Recd, C. E., Licbtenstein, L. M. et al. (1975): J.
~ponses. This is perhaps due to saturation of IgE binding Amer. med. Ass., 231, 1154.
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~ites by high levels of circulating venom. This study does, Joh"s Hopk. med. J., 142, I.
Serum Ferritin Estimation in the Assessment of Iron Stores
in Severe Iron Deficiency Anaemia in Pregnancy and the
Response to Treatment
M. L. SEGALL, J. DOMMISSE, E. D. DU TOIT, D. A. DAVEY, H. DE V. HEESE
SUMMARY in pregnancy. The response to oral or intravenous iron
therapy was monitored in 18 of these patients.
Serum ferritin estimation was used to determine the iron
The results in all cases indica~ed deficient iron stores.
stores in 55 patients with severe iron deficiency anaemia Rep!enishmenl of iron stores was significantly greater in
those patients trented with parenteral iron. Th's may be
I)epartment of Paediatrics and Child Health, Red Cross War the treatment of choice for severe iron deficiency anaemia
Memorial Children's Hospital and University of Cape Town during pregnancy.
M. L. SEGALL, M.B. CH-B., F.C.P., Consultant (Present address:
Department of Pediatrics, UCD - Sacramento Medical Center, S. A fr. med. J.• 55, 287 (1979).
Sacramenta, California, USA)
H. DE V. HEESE, 1\1.0., B.SC., F.B.C.P., D.C.H .. Professor alld
Head Inadequate iron nutrition and the increased demands of
pregnancy often result in a negative iron balance. The
I)epartmeilt of Obstetrics and Gynaecology, Groote SChUOT clinical implications of mild anaemia in pregnancy are un-
Hospital and University of Cape Town
certain, but severe iron deficiency anaemia, the end-stage
.I. DO 1MISSE, M.B. CH.B., F.R.C.O.G., Consultant
I). A. DAVEY, M.B. B.S., PH.D., F.B.C.O.G., Professor and Head of this imbalance, is associated with an increased mater-
nal mortality and morbidity.'
(::ape Provincial Blood Grouping Laboratory, Cape Town The highest incidence of severe anaemia occurs in lower
~=. D. DU TOn, M.B. CH. B., M.D., Principal Medical Officer socio-economic groups and developing countries.' In the
[)ate received: 13 October 1978. Cape Town area, approximately 0,5% of pregnant women