Author: V. Dimov, M.D., Assistant Professor, Allergist/Immunologist, University of Chicago; A. Bewtra, M.D., M.B.B.S., Professor, Creighton University Division of Allergy & Immunology
Reviewer: S. Randhawa, M.D., Allergist/Immunologist, Fort Lauderdale, Florida
A 26-year-old Caucasian female is referred to the allergy clinic for skin prick testing for suspected semen allergy. For the last 5 years, she reports symptoms when she has unprotected intercourse with her husband. She has no symptoms when she has a protected intercourse. The typical symptoms are burning, swelling, and redness outside the vaginal area that start 10 to 15 minutes after intercourse and last from hours to days. The patient reports that on the first day of intercourse, she will have symptoms for a few hours, but if she has intercourse the very next day, then the symptoms are worse and last for days rather than hours. She and her husband expressed an interest in conceiving and had already seen an OB/GYN physician who prescribed Clomid (Clomiphene). Since then the patient had a menstrual period and she is here for skin prick testing to semen allergy. Her husband brought a container with previously collected semen fluid to the clinic.
Past medical history (PMH)
Mild asthma, allergic rhinitis.
Veramyst (fluticasone) nasal spray, albuterol prn (uses very rarely), Clomid, loratidine (stopped six days ago for the skin prick testing).
Stable vital signs (VSS), normal physical examination.
What would you do next?
Skin prick testing with positive control with histamine, negative control with normal saline and semen fluid.
Test results: The patient’s skin prick testing showed a positive skin control with histamine, a wheal of 5 x 5 mm, a flare of 15 x 15 mm, a negative control with saline 0 x 0 mm for both wheal and flare, and and a positive reaction to the semen fluid with 4 x 3 mm for the wheal and 10 x 7 mm for the flare. We read the test after 15 minutes.
What would you recommend for this patient?
The patient has a diagnosis of semen allergy confirmed by medical history, symptoms timeline and positive skin prick testing.
In order to avoid symptoms, we advised the patient and her husband to have protected sexual intercourse with condoms in the future.
In terms of conceiving a baby, we recommend that she should work closely with her OB/GYN and once she begins to have ovulatory cycles, as determined by a pelvic ultrasound, the plan is for her to be placed on prednisone for 7 to 10 days around the expected time of ovulation. A possible consideration, if this does not work, would be intrauterine insemination with washed semen.
After she finalizes her plan about conception, we will change her intranasal steroid to budesonide, which is a category B medication in pregnancy. She is to follow up prn with us regarding further follow-up with her OB/GYN and the allergy clinic here.
What did we learn from this case?
Women with seminal plasma protein allergy (SPPA) have an immunologic response to human semen. The immunological mechanism of semen allergy is a type I hypersensitivity reactions.
Symptoms vary from local inflammation and pruritus to systemic anaphylaxis after exposure. The first case was documented in Germany in 1958.
Patients with SPPA often have recurrent vaginitis associated with intercourse and are unresponsive to traditional therapies. Semen allergy should be on the list of differential diagnoses for recurrent vaginitis in sexually active women. SPPA may also present as ‘vulvar vestibulitis syndrome’ or ‘burning semen syndrome’.
The gold standard of diagnosis is absence of symptoms with condom use.
Treatment may involve artificial insemination for those seeking pregnancy, oral corticosteroids, immunotherapy, or antihistamines, rather than use of a condom or abstinence.
Systemic and localized reactions can be prevented by use of condoms. However, partners should always be instructed on the use of an automatic epinephrine injector (EpiPen) and it should be available.
In patients who wish to conceive, and/or condoms are unacceptable, immunotherapy with seminal fluid can be performed. Alternatively, patients can conceive by artificial insemination with washed spermatozoa.
Here are the suggested diagnostic steps from AAAAI Ask the Expert and Dr. Bernstein (http://buff.ly/16yXcPD):
1) Test by PST to whole seminal fluid. This requires letting the ejaculate liquefy for 30 min and centrifuge for 10 minutes to separate seminal fluid from spermatozoa. Also test sexual partner as a negative control. You do not have to sterilize the seminal fluid for prick testing. Intracutaneous testing to whole seminal fluid should not be performed as it will cause an irritant response.
2) Both the patient and her sexual partner should be screened for STD's.
3) Some women have trouble with all men whereas other have symptoms with only one.
4) For localized seminal plasma hypersensitivity, skin testing is not always concordant with serologic testing. Patients can send their serum and their sexual partner's serum and a 5 day pooled ejaculate to Dr. Bernstein's laboratory to test for sIgE to whole seminal plasma.
5) There is cross reactivity between dog allergens and seminal plasma.
6) Patients with localized seminal plasma hypersensitivity should first undergo intravaginal graded challenge; dilute whole seminal fluid with sterile water to 1:100,000 dilution and instill 10 cc of volume intravaginally every 10-15 minutes up to a `1:1 dilution to see if this alleviates symptoms. There are reported cases that this may be effective. If not then the patient may be a candidate for subcutaneous desensitization to relevant fractionated seminal plasma proteins.
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Seminal Fluid. AAAAI Ask the Expert, 2003.
Immunologic disorders of the female and male reproductive tract. Annals of Allergy, Asthma & Immunology, Volume 108, Issue 6 , Pages 390-395, June 2012.
IgE-Mediated Allergy against Human Seminal Plasma. Weidinger S, Ring J, Köhn J. Immunology of Gametes and Embryo Implantation. Chem Immunol Allergy. Basel, Karger, 2005, vol 88, pp 128-138.
Allergy to human seminal plasma: a presentation of six cases. Kroon S. Acta Derm Venereol. 1980;60(5):436-9.
Diagnosis and treatment of human seminal plasma hypersensitivity. Lee-Wong M, Collins JS, Nozad C, Resnick DJ. Obstet Gynecol. 2008 Feb;111(2 Pt 2):538-9.
Anaphylaxis to husband's seminal plasma and treatment by local desensitization. Lee J, Kim S, Kim M, Chung YB, Huh JS, Park CM, Lee KH, Kim JH. Clin Mol Allergy. 2008 Dec 5;6:13.
Management of seminal fluid hypersensitivity reactions. AAAAI Ask the Expert, 2011.
The Diagnosis and Management of Anaphylaxis Practice Parameter: 2010 Update. J Allergy Clin Immunol 2010; 126(3):477-522. The segment dealing with seminal fluid allergy begins on page 480.e17, under the heading "Seminal Fluid Anaphylaxis."
Frequent Sex Cures Women's Semen Allergy. Fox News, 11/2008.
Woman discovers she's allergic to her husband. Daily Mail, 2009.
A 5-Year Followup of Human Seminal Plasma Allergy http://bit.ly/M3mDMX
Involvement of the dog allergen Can f 5 in a Case of Human Seminal Plasma Allergy http://goo.gl/cQSvj
Successful intravaginal graded challenge after a systemic reaction with skin prick testing to seminal fluid http://buff.ly/XKq4Ak
Vaginal pain with intercourse: is it seminal fluid allergy? AAAAI Ask the Expert answers: http://buff.ly/16yXcPD
Skin test may not be reliable for diagnosis of sensitization to seminal fluid proteins. Caused by PGs rather than IgE http://buff.ly/1wES08b