- Email: [email protected]
Ocular challenge and hyperresponsiveness to histamine in patients with allergic conjunctivitis
J ALLERGY CLIN IMMUNOL VOLUME 91, NUMBER 6
strong enough to cause perceivable symptoms, but it can induce a refractory period. The mechanism responsible for this is unknown. Prostaglandin release might be involved, since in patients with asthma, refractoriness can be inhibited by indomethacin.3 Although we cannot explain the exact pathomechanism of the refractory period, it was satisfying to make use of it. Curing a disease with early morning exercise is probably the most wholesome therapy conceivable.
Zuberbier,
the Allergy and Clinical Immunology Service, Department of Internal Medicine-DI.M.I., University of Genoa, Italy. Reprint requests: G. Walter Canonica, MD, Allergy and Clinical Immunology Service, Department of Internal Medicine-DI.M.I., Viale Benedetto XV, 6, 16132 Genoa, Italy. J ALLERGY CLIN IMMUNOL 1993;91:1227-30 Copyright 0 1993 by Mosby-Year Book, Inc. 0091-6749193 $1.00 + .lO 1154145633
Czarnetzki
1. Casale TB, Keahey TM, Kaliner M. Exercise-induced anaphylactic syndromes: insights into diagnostic and pathophysiologic features. JAMA 1986;255:2049-53. 2. Bierman CW. Management of exercise-induced asthma. Ann Allergy 1992;68:119-22. 3. O’Byme PM, Jones GL. The effect of indomethacin on exerciseinduced bronchoconstriction and refractoriness after exercise. Am Rev Respir Dis 1986;134:69-72.
to
G. Ciprandi, MD, S. Buscaglia, MD, G. P. Pesce, BS, M. Bagnasco, G. W. Canonica, MD Genoa, Italy
From
and
REFERENCES
Ocular challenge and hyperresponsiveness histamine in patients with allergic conjunctivitis
Nonspecific hyperreactivity to physical, chemical, and pharmacologic agents is a common characteristic of allergic subjects, which is strictly related to the inflammatory events consequent to allergic reacti0n.l. ’ Histamine challenge is a common nonspecific test to evaluate hyperreactivity in subjects with asthma and rhinitis.’ Recently, Bonini et a1.3 demonstrated a conjunctival hyperresponsiveness to histamine in patients with vernal conjunctivitis by evaluating conjunctival hyperemia. We evaluated the possible evidence of ocular hyperresponsiveness to histamine in patients with allergic conjunctivitis on the basis of several parameters: clinical evidence (i.e., ocular hyperemia), cellular inflammatory infiltrate, and CD54 expression on conjunctival epithelial cells. Particularly, we focused our attention on CD54 (Intra-
Bohm,
Abbreviations used Dp: Dennatophagoides Par j: Pat&aria judaica
MD, and
pteronyssinus
PD: Provoking dose
cellular Adhesion Molecule-l), an adhesion molecule with an immunoglobulin-like structure present on activated immunocompetent cells, endothelia, and inflamed epithelium. We have recently demonstrated CD54 expression on conjunctival epithelial cells after allergen challenge in allergic subjects.“ METHODS
Twenty patients who were free of symptoms (11 men and 9 women, aged 18 to 54 years) with a previously documented diagnosis of allergic conjunctivitis due to Parieturiu Judaica (Par j) (10 subjects) or Dermztophugoides pteronyssinus (Dp) (10 subjects) were selected. All allergic subjects had positive history (for at least 2 years), positive skin prick test results (more than + + +, histamine + + +), positive RAST results (more than class III) and positive allergen-specific conjuncti-
1227
1228
Ciprandi
et al,
J ALLERGY CLIN IMMUNOL JUNE 1993
0.5
-
0.4
-
0.3
-
0.2
-
kl E Q
0.1
-
k
0.011-
.g E c:
0.0: I-
-g
0.0: j-
-E
O 0
0
0.0.
00 0.0
0.05a-
O.Ofi00
00
00
0.04I-
0
0.0: S-
0
0.02I-
0
00 0
0
0.01l-
0.0
0
O.OO!a-0.00130.00: IHealthy volunteers
Par J sensitive patients
Dp sensitive patients
FIG. 1. Histamine chlorhydrate PD in healthy volunteers, Par-j-sensitive patients, and Dpsensitive patients. Intergroup comparison performed with Student’s t test for independent samples provided the following statistical information: Dp-sensitive patients versus Par j-sensitive patients, p < 0.03; Dp-sensitive patients versus healthy volunteers, p < 0.01; Par-j-sensitive patients versus healthy volunteers, p = NS.
val challenge results for the specific allergen. Ten healthy volunteers (two men and eight women, aged 21 to 34 years) with no history of allergy were included as control subjects. On admission, allergic subjects and healthy volunteers did not have evidence of any baseline asymptomatic conjunctival hyperemia as determined by ophthalmologic examination. All patients had no other ocular diseases and did not wear contact lenses. No topical or systemic drug was allowed for 1 month before the study period. The study was performed in the off-pollen season. All subjects gave informed consent, and the trial was approved by the Department’s ethical committee. According to our previous reports, conjunctival challenge and conjunctival scrapings were per-
formed at baseline and 30 minutes after challenge.“ Ten microliters of increasing doses of histamine chlorhydrate (kindly provided by Bayropharm-DHS, Milan, Italy) were instilled into the lower conjunctival sac in each subject’s right eye (doses ranged from 0.005 to 0.3 mg/ml diluted in saline albumin solution, 0.03%) at lo-minute intervals, until a provoking dose (PD) was reached. The PD was arbitrarily defined as the minimal histamine chlorhydrate dilution able to elicit a clinical response expressed by conjunctival hyperemia intensity (more than +2, according to Abelson-Udell-Weston classification).5 In the left eye 10 ~1 of saline albumin solution (used to dilute histamine) was instilled as control at the same intervals.
J ALLERGY CLIN IMMUNOL VOLUME 91, NUMBER 6
The clinical reaction to the stimulus was assessed in blinded fashion by two investigators, by means of penlight examination; conjunctival hyperemia was evaluated according to AbelsonUdell-Weston classification.’ Conjunctival scraping was performed according to our standard protocol to evaluate cellular infiltrate.4 CD54 expression on conjunctival epithelium was performed by means of an immunoenzymatic alkaline phosphatase-monoclonal anti-alkaline phosphatase complex procedure, which was modified from the method of Cordell et a1.6with an appropriate dilution of purified CD54 monoclonal antibody (1 mg/ml, 84H10, IgG,; Immunotech S. A., Marseille Cedex, France). Scoring of cellular infiltrate and CD54 expression was assessed as previously described. Statistical analysis of results was performed by the Mann-Whitney U test, Wilcoxon test, and Student’s t test for independent samples, as appropriate. RESULTS At baseline healthy volunteers and Par-j-sensitive subjects did not show any difference as far as clinical and cytologic parameters (absence of inflammatory infiltrate and absence of CD54 expression on epithelium) are concerned (Fig. 1). On the contrary, at baseline Dp-sensitive patients had evidence of a mild cellular infiltrate (mainly neutrophils and lymphocytes) that was significantly higher compared with those of healthy volunteers and Par-j-sensitive patients @ < 0.002) as determined by Mann-Whitney U test. Moreover, a mild CD54 expression on conjunctival epithelium, which was significantly higher compared with those of healthy volunteers and Par-j-sensitive patients, was evident in Dpsensitive patients (p < 0.002). All subjects in the study showed a statistically significant clinical reaction compared with baseline after challenge with histamine chlorhydrate @ < 0.002, by Wilcoxon test); PD ranged from 0.01 to 0.3 mglml. The PD able to elicit hyperemia was significantly lower in Dp-sensitive patients than in Par-j-sensitive patients (p c 0.03) and in healthy volunteers (p < 0.01) as determined by Student’s t test, whereas no significant difference was evident between Par-j-sensitive patients and healthy volunteers. Neither cellular infiltration nor CD54 expression on conjunctival epithelium was detected in healthy volunteers and Par-j-
Ciprandi
et al.
1229
sensitive patients after histamine challenge. In Dp-sensitive patients cellular infiltrate and CD54 expression on conjunctival epithelium were not affected by histamine challenge. No ocular reaction appeared in the contralateral eye that was challenged with diluent (saline albumin solution). DISCUSSION The present report confirms that histamine challenge induces a vascular reactivity, but it demonstrates that histamine is not able to induce an inflammatory response in the eye model and CD54 expression on epithelium. Also, the presence of conjunctival hyperreactivity to histamine appeared only in Dp-sensitive patients. This phenomenon is likely to be related to a minimal persistent inflammation, which is present in Dpsensitive patients: this is reminiscent of the findings of Bonini et a1.3in vernal conjunctivitis, which is characterized by a chronic inflammatory process. As a matter of fact, we found that a cellular inflammatory infiltrate is already present and a mild CD54 expression is also evident on conjunctival epithelium in basal conditions in Dp-sensitive individuals (although completely symptomfree as far as the conjunctiva is concerned): histamine challenge does not affect either of these parameters in our experience. On the other hand, out of pollen season, Parj-sensitive patients did not show either inflammatory infiltrate or CD54 expression on conjunctival epithelium, and consequently, they demonstrated lack or low degree of hyperactivity. These data fit very well with what has been previously reported in patients with pollinosis as far as the nasal and bronchial models are concerned.‘, * In conclusion, our data demonstrate the presence of hyperreactivity to histamine chlorhydrate in allergic conjunctivitis only when a previous inflammation, although minimal, is present (i.e., due to Dp) and suggest further studies concerning the role of the minimal persistent inflammation in the development and possible maintenance of the allergic process. REFERENCES
1. Gerth Van Wijk R. Nasal hyperreactivity: its pathogenesis and clinical significance. Clin Exp Allergy 1991;21:661-7. 2. Vries K. Clinical significance of bronchial hyperresponsiveness. In: Nadel JA, Pauwels R, Snashall PD, eds. Bronchial hyperresponsiveness. Oxford: Blackwell Scientific Publications, 1987:359-72.
Ciprandi
et al.
J ALLERGY CLIN IMMUNOL JUNE 1993
3. Bonini ST, Bonini SE, Schiavone M, Centofanti M, Allansmith M, Bucci MG. Conjunctival hyperresponsiveness to ocular histamine challenge in patients with vernal conjunctivitis. J ALLERGY GIN IMMUNOL1992;89:103-7. 4. Ciprandi G, Buscaglia S, Pesce GP, Villaggio B, Bagnasco M, Canonica GW. Allergic subjects express Intercellular Adhesion Molecule-l (ICAM- or CD54) on epithelial cells of conjunctiva after allergen challenge. J ALLERGY CLIN IMMUNOL 1993;91:783-92.
Local intravaginal seminal fluid Steven M. Matloff,
desensitization
to
MD Boston,Mass.
This report describes a patient with local hypersensitivity to seminal fluid who was successfully treated with local intravaginal desensitization. CASE REPORT A 28-year-old married woman was referred for evaluation of a 4-year history of postcoital vaginal and perivaginal swelling that occurred immediately after ejaculation during intercourse. The patient has had one sexual partner for the past 6 years and first noticed this problem 2 years after she began having intercourse with this partner. The vaginal and perivaginal angioedema typically persisted for 12 to 24 hours after intercourse and would spontaneously resolve with no specific therapy. One year ago, these episodes began to get more severe and were associated with severe itching, burning, and discomfort. Warm baths immediately after intercourse helped to accelerate resolution. The reactions were not associated with other symptoms of systemic anaphylaxis. The patient was only taking an oral contraceptive. Her husband was not taking medication. The patient was advised to use condoms and had From the Department of Allergy, Harvard Community Health Plan, Boston. Reprint requests: Steven M. Matloff, MD, Harvard Community Health Plan, 291 Independence Dr., West Roxbury, MA 02167. J ALLERGY CLIN hMUNOL 1993;91:1230-1 Copyright 0 1993 by Mosby-Year Book, Inc. 0091-6749/93 $1.00 + .lO l/54/46299
1230
5. Abelson MB, Udell IJ, Weston JH. Standardization of ocular surface injection intensity. Ann Ophtalmol 1981;13: 1225. 6. Cordell JL, Falini B, Erber WN, et al. Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem 1984; 32~219-29.
immediate resolution of all postcoital symptoms for several months. Although intercourse with condoms was always tolerated without adverse effects, the patient and her husband did not find this to be a satisfactory solution. A skin prick test with her husband’s fresh undiluted seminal fluid demonstrated a small positive :%vheal and flare (mean wheal diameter, 5 mm x mean flare diameter, 30 mm), with a positive histamine control (5 mm x 40 mm) and negative saline control. An ELISA, in which previously described methods were used,l was negative for serum IgE to seminal fluid antigen. An active fraction of seminal fluid protein was used for the assay. Local desensitization was performed by depositing progressively greater concentrations of her husband’s semen intravaginally at 20-minute intervals (Table I). No local reactions occurred at dilutions of 1: 1,000, 1: 100, and 1: 10. After the undiluted semen sample was deposited, a slight degree of swelling of the labia minora occurred after 15 to 20 minutes, with minimal burning and itching at the introitus. The patient judged the reaction to be minimal, relative to her previous reactions, and it lasted for only 30 minutes. The patient was instructed to have frequent intercourse without condoms to maintain the desensitized state. She had intercourse every 24 to 48 hours for 2 months without experiencing any local perivaginal angioedema, pruritis, or discomfort. A lo-day hiatus in this routine resulted in return of symptoms. The desensitization proce-
strong enough to cause perceivable symptoms, but it can induce a refractory period. The mechanism responsible for this is unknown. Prostaglandin release might be involved, since in patients with asthma, refractoriness can be inhibited by indomethacin.3 Although we cannot explain the exact pathomechanism of the refractory period, it was satisfying to make use of it. Curing a disease with early morning exercise is probably the most wholesome therapy conceivable.
Zuberbier,
the Allergy and Clinical Immunology Service, Department of Internal Medicine-DI.M.I., University of Genoa, Italy. Reprint requests: G. Walter Canonica, MD, Allergy and Clinical Immunology Service, Department of Internal Medicine-DI.M.I., Viale Benedetto XV, 6, 16132 Genoa, Italy. J ALLERGY CLIN IMMUNOL 1993;91:1227-30 Copyright 0 1993 by Mosby-Year Book, Inc. 0091-6749193 $1.00 + .lO 1154145633
Czarnetzki
1. Casale TB, Keahey TM, Kaliner M. Exercise-induced anaphylactic syndromes: insights into diagnostic and pathophysiologic features. JAMA 1986;255:2049-53. 2. Bierman CW. Management of exercise-induced asthma. Ann Allergy 1992;68:119-22. 3. O’Byme PM, Jones GL. The effect of indomethacin on exerciseinduced bronchoconstriction and refractoriness after exercise. Am Rev Respir Dis 1986;134:69-72.
to
G. Ciprandi, MD, S. Buscaglia, MD, G. P. Pesce, BS, M. Bagnasco, G. W. Canonica, MD Genoa, Italy
From
and
REFERENCES
Ocular challenge and hyperresponsiveness histamine in patients with allergic conjunctivitis
Nonspecific hyperreactivity to physical, chemical, and pharmacologic agents is a common characteristic of allergic subjects, which is strictly related to the inflammatory events consequent to allergic reacti0n.l. ’ Histamine challenge is a common nonspecific test to evaluate hyperreactivity in subjects with asthma and rhinitis.’ Recently, Bonini et a1.3 demonstrated a conjunctival hyperresponsiveness to histamine in patients with vernal conjunctivitis by evaluating conjunctival hyperemia. We evaluated the possible evidence of ocular hyperresponsiveness to histamine in patients with allergic conjunctivitis on the basis of several parameters: clinical evidence (i.e., ocular hyperemia), cellular inflammatory infiltrate, and CD54 expression on conjunctival epithelial cells. Particularly, we focused our attention on CD54 (Intra-
Bohm,
Abbreviations used Dp: Dennatophagoides Par j: Pat&aria judaica
MD, and
pteronyssinus
PD: Provoking dose
cellular Adhesion Molecule-l), an adhesion molecule with an immunoglobulin-like structure present on activated immunocompetent cells, endothelia, and inflamed epithelium. We have recently demonstrated CD54 expression on conjunctival epithelial cells after allergen challenge in allergic subjects.“ METHODS
Twenty patients who were free of symptoms (11 men and 9 women, aged 18 to 54 years) with a previously documented diagnosis of allergic conjunctivitis due to Parieturiu Judaica (Par j) (10 subjects) or Dermztophugoides pteronyssinus (Dp) (10 subjects) were selected. All allergic subjects had positive history (for at least 2 years), positive skin prick test results (more than + + +, histamine + + +), positive RAST results (more than class III) and positive allergen-specific conjuncti-
1227
1228
Ciprandi
et al,
J ALLERGY CLIN IMMUNOL JUNE 1993
0.5
-
0.4
-
0.3
-
0.2
-
kl E Q
0.1
-
k
0.011-
.g E c:
0.0: I-
-g
0.0: j-
-E
O 0
0
0.0.
00 0.0
0.05a-
O.Ofi00
00
00
0.04I-
0
0.0: S-
0
0.02I-
0
00 0
0
0.01l-
0.0
0
O.OO!a-0.00130.00: IHealthy volunteers
Par J sensitive patients
Dp sensitive patients
FIG. 1. Histamine chlorhydrate PD in healthy volunteers, Par-j-sensitive patients, and Dpsensitive patients. Intergroup comparison performed with Student’s t test for independent samples provided the following statistical information: Dp-sensitive patients versus Par j-sensitive patients, p < 0.03; Dp-sensitive patients versus healthy volunteers, p < 0.01; Par-j-sensitive patients versus healthy volunteers, p = NS.
val challenge results for the specific allergen. Ten healthy volunteers (two men and eight women, aged 21 to 34 years) with no history of allergy were included as control subjects. On admission, allergic subjects and healthy volunteers did not have evidence of any baseline asymptomatic conjunctival hyperemia as determined by ophthalmologic examination. All patients had no other ocular diseases and did not wear contact lenses. No topical or systemic drug was allowed for 1 month before the study period. The study was performed in the off-pollen season. All subjects gave informed consent, and the trial was approved by the Department’s ethical committee. According to our previous reports, conjunctival challenge and conjunctival scrapings were per-
formed at baseline and 30 minutes after challenge.“ Ten microliters of increasing doses of histamine chlorhydrate (kindly provided by Bayropharm-DHS, Milan, Italy) were instilled into the lower conjunctival sac in each subject’s right eye (doses ranged from 0.005 to 0.3 mg/ml diluted in saline albumin solution, 0.03%) at lo-minute intervals, until a provoking dose (PD) was reached. The PD was arbitrarily defined as the minimal histamine chlorhydrate dilution able to elicit a clinical response expressed by conjunctival hyperemia intensity (more than +2, according to Abelson-Udell-Weston classification).5 In the left eye 10 ~1 of saline albumin solution (used to dilute histamine) was instilled as control at the same intervals.
J ALLERGY CLIN IMMUNOL VOLUME 91, NUMBER 6
The clinical reaction to the stimulus was assessed in blinded fashion by two investigators, by means of penlight examination; conjunctival hyperemia was evaluated according to AbelsonUdell-Weston classification.’ Conjunctival scraping was performed according to our standard protocol to evaluate cellular infiltrate.4 CD54 expression on conjunctival epithelium was performed by means of an immunoenzymatic alkaline phosphatase-monoclonal anti-alkaline phosphatase complex procedure, which was modified from the method of Cordell et a1.6with an appropriate dilution of purified CD54 monoclonal antibody (1 mg/ml, 84H10, IgG,; Immunotech S. A., Marseille Cedex, France). Scoring of cellular infiltrate and CD54 expression was assessed as previously described. Statistical analysis of results was performed by the Mann-Whitney U test, Wilcoxon test, and Student’s t test for independent samples, as appropriate. RESULTS At baseline healthy volunteers and Par-j-sensitive subjects did not show any difference as far as clinical and cytologic parameters (absence of inflammatory infiltrate and absence of CD54 expression on epithelium) are concerned (Fig. 1). On the contrary, at baseline Dp-sensitive patients had evidence of a mild cellular infiltrate (mainly neutrophils and lymphocytes) that was significantly higher compared with those of healthy volunteers and Par-j-sensitive patients @ < 0.002) as determined by Mann-Whitney U test. Moreover, a mild CD54 expression on conjunctival epithelium, which was significantly higher compared with those of healthy volunteers and Par-j-sensitive patients, was evident in Dpsensitive patients (p < 0.002). All subjects in the study showed a statistically significant clinical reaction compared with baseline after challenge with histamine chlorhydrate @ < 0.002, by Wilcoxon test); PD ranged from 0.01 to 0.3 mglml. The PD able to elicit hyperemia was significantly lower in Dp-sensitive patients than in Par-j-sensitive patients (p c 0.03) and in healthy volunteers (p < 0.01) as determined by Student’s t test, whereas no significant difference was evident between Par-j-sensitive patients and healthy volunteers. Neither cellular infiltration nor CD54 expression on conjunctival epithelium was detected in healthy volunteers and Par-j-
Ciprandi
et al.
1229
sensitive patients after histamine challenge. In Dp-sensitive patients cellular infiltrate and CD54 expression on conjunctival epithelium were not affected by histamine challenge. No ocular reaction appeared in the contralateral eye that was challenged with diluent (saline albumin solution). DISCUSSION The present report confirms that histamine challenge induces a vascular reactivity, but it demonstrates that histamine is not able to induce an inflammatory response in the eye model and CD54 expression on epithelium. Also, the presence of conjunctival hyperreactivity to histamine appeared only in Dp-sensitive patients. This phenomenon is likely to be related to a minimal persistent inflammation, which is present in Dpsensitive patients: this is reminiscent of the findings of Bonini et a1.3in vernal conjunctivitis, which is characterized by a chronic inflammatory process. As a matter of fact, we found that a cellular inflammatory infiltrate is already present and a mild CD54 expression is also evident on conjunctival epithelium in basal conditions in Dp-sensitive individuals (although completely symptomfree as far as the conjunctiva is concerned): histamine challenge does not affect either of these parameters in our experience. On the other hand, out of pollen season, Parj-sensitive patients did not show either inflammatory infiltrate or CD54 expression on conjunctival epithelium, and consequently, they demonstrated lack or low degree of hyperactivity. These data fit very well with what has been previously reported in patients with pollinosis as far as the nasal and bronchial models are concerned.‘, * In conclusion, our data demonstrate the presence of hyperreactivity to histamine chlorhydrate in allergic conjunctivitis only when a previous inflammation, although minimal, is present (i.e., due to Dp) and suggest further studies concerning the role of the minimal persistent inflammation in the development and possible maintenance of the allergic process. REFERENCES
1. Gerth Van Wijk R. Nasal hyperreactivity: its pathogenesis and clinical significance. Clin Exp Allergy 1991;21:661-7. 2. Vries K. Clinical significance of bronchial hyperresponsiveness. In: Nadel JA, Pauwels R, Snashall PD, eds. Bronchial hyperresponsiveness. Oxford: Blackwell Scientific Publications, 1987:359-72.
Ciprandi
et al.
J ALLERGY CLIN IMMUNOL JUNE 1993
3. Bonini ST, Bonini SE, Schiavone M, Centofanti M, Allansmith M, Bucci MG. Conjunctival hyperresponsiveness to ocular histamine challenge in patients with vernal conjunctivitis. J ALLERGY GIN IMMUNOL1992;89:103-7. 4. Ciprandi G, Buscaglia S, Pesce GP, Villaggio B, Bagnasco M, Canonica GW. Allergic subjects express Intercellular Adhesion Molecule-l (ICAM- or CD54) on epithelial cells of conjunctiva after allergen challenge. J ALLERGY CLIN IMMUNOL 1993;91:783-92.
Local intravaginal seminal fluid Steven M. Matloff,
desensitization
to
MD Boston,Mass.
This report describes a patient with local hypersensitivity to seminal fluid who was successfully treated with local intravaginal desensitization. CASE REPORT A 28-year-old married woman was referred for evaluation of a 4-year history of postcoital vaginal and perivaginal swelling that occurred immediately after ejaculation during intercourse. The patient has had one sexual partner for the past 6 years and first noticed this problem 2 years after she began having intercourse with this partner. The vaginal and perivaginal angioedema typically persisted for 12 to 24 hours after intercourse and would spontaneously resolve with no specific therapy. One year ago, these episodes began to get more severe and were associated with severe itching, burning, and discomfort. Warm baths immediately after intercourse helped to accelerate resolution. The reactions were not associated with other symptoms of systemic anaphylaxis. The patient was only taking an oral contraceptive. Her husband was not taking medication. The patient was advised to use condoms and had From the Department of Allergy, Harvard Community Health Plan, Boston. Reprint requests: Steven M. Matloff, MD, Harvard Community Health Plan, 291 Independence Dr., West Roxbury, MA 02167. J ALLERGY CLIN hMUNOL 1993;91:1230-1 Copyright 0 1993 by Mosby-Year Book, Inc. 0091-6749/93 $1.00 + .lO l/54/46299
1230
5. Abelson MB, Udell IJ, Weston JH. Standardization of ocular surface injection intensity. Ann Ophtalmol 1981;13: 1225. 6. Cordell JL, Falini B, Erber WN, et al. Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem 1984; 32~219-29.
immediate resolution of all postcoital symptoms for several months. Although intercourse with condoms was always tolerated without adverse effects, the patient and her husband did not find this to be a satisfactory solution. A skin prick test with her husband’s fresh undiluted seminal fluid demonstrated a small positive :%vheal and flare (mean wheal diameter, 5 mm x mean flare diameter, 30 mm), with a positive histamine control (5 mm x 40 mm) and negative saline control. An ELISA, in which previously described methods were used,l was negative for serum IgE to seminal fluid antigen. An active fraction of seminal fluid protein was used for the assay. Local desensitization was performed by depositing progressively greater concentrations of her husband’s semen intravaginally at 20-minute intervals (Table I). No local reactions occurred at dilutions of 1: 1,000, 1: 100, and 1: 10. After the undiluted semen sample was deposited, a slight degree of swelling of the labia minora occurred after 15 to 20 minutes, with minimal burning and itching at the introitus. The patient judged the reaction to be minimal, relative to her previous reactions, and it lasted for only 30 minutes. The patient was instructed to have frequent intercourse without condoms to maintain the desensitized state. She had intercourse every 24 to 48 hours for 2 months without experiencing any local perivaginal angioedema, pruritis, or discomfort. A lo-day hiatus in this routine resulted in return of symptoms. The desensitization proce-