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Objective: Women have exhibited anaphylaxis, urticaria/angioedema, and autoimmune progesterone dermatitis (APD) coinciding with the progesterone premenstrual rise. We report a detailed immunological evaluation of such a woman responsive to a gonadotropin hormone-releasing agonist (GHRA)., Methods: Skin testing, enzyme-linked immunosorbent assays (ELISAs), leukocyte histamine release (LHR), and inhibition assays were performed to demonstrate progesterone immunoresponsiveness., Results: Serum specific-progesterone immunoglobulin G (IgG) and IgE were detected initially and disappeared 6 months after GHRA treatment. Dose-response LHR using patient basophils was observed for different hormones but after 3 months persisted only for 5β-pregnanediol. Preincubation with mouse antiprogesterone monoclonal antibody (PmAb) or mifepristone, a progesterone inhibitor, over a range of doses inhibited specific progesterone-induced LHR. Experiments with varying progesterone concentrations and a fixed dose of anti-IgE resulted in 100% LHR at a concentration as low as 0.016 nmol/mL, which, without anti-IgE, failed to release histamine., Conclusions: This is the first report of combined recurrent anaphylaxis, cyclic urticaria/angioedema, and APD induced by immunoresponsiveness to progesterone.

A 24-year-old white woman reported sexual intercourse-related pruritus, hives, wheezing, and dyspnea within 5 minutes after ejaculation. Systemic reactions (SRs) were prevented by use of condoms. Prick testing confirmed sensitization to five Sephadex G-100-separated fractions of her husband's seminal plasma. The intradermal end point threshold concentrations (ETC) were 10(-4) and 10(-1) micrograms of protein per milliliter to fractions 2 and 3, respectively. Leukocyte histamine release studies exhibited 100% release to fraction 2 and 37% release to fraction 3. A 2-day protocol of rapid immunotherapy (IT) was performed with subcutaneous incremental doses of human seminal plasma (HuSePl) fractions 2 and 3. The patient experienced an SR after receiving a cumulative dose of 38.55 micrograms of fraction 2 on day 1. On day 2, rapid IT with fraction 2 was administered until the patient experienced a mild SR after having received a cumulative dose of 102.8 micrograms. There was a one-log10 increase in the intradermal ETC to both fractions 2 and 3 at the end of day 2. IT was continued three times weekly for 4 months until the patient tolerated 100 micrograms doses of both fractions 2 and 3. At 4 months, coitus was resumed without SRs, and HuSePl IT was stopped. The intradermal ETC to fractions 1, 3, 4, and 5 was increased 6 months after cessation of HuSePl injections, but there was a one-log decrease in the ETC to fraction 2. Our experience demonstrated that systemic tolerance can be achieved by parenteral administration of selected HuSePl fractions. Partial immunologic desensitization of patients with anaphylactic sensitivity can be achieved.(ABSTRACT TRUNCATED AT 250 WORDS)

The risk of anaphylaxis in candidates for chemonucleolysis for herniated lumbar discs is approximately 1%. An investigation was designed to eliminate or reduce the incidence of chymopapain anaphylaxis. The procedure was to restrict chemonucleolysis to patients who are prick test-negative to chymopapain at a concentration of 10 mg/ml. The authors skin-tested 292 chemonucleolysis candidates; five were positive and 287 were negative. None of the positive patients were injected with chymopapain. There were no instances of unequivocal chymopapain anaphylaxis in the skin test-negative group. This 0% incidence of anaphylaxis in skin test-negative patients was compared with a population estimate of 1%, based on historical data. The resulting value of p = 0.08 value fell short of the conventional level of significance of 0.05. The p value will reach 0.05 when the series of skin test-negative patients without anaphylaxis reaches 360. It is important that this information is readily available to physicians concerned about anaphylactic reactions to chymopapain.

Anaphylactic sensitivity to her husband's seminal fluid occurred in a 46-year-old woman six weeks after a hysterectomy. Her husband was azoospermic as a result of an elective vasectomy. A pooled sample of his seminal fluid was used for skin and laboratory tests. Fractionating (Sephadex G100) chromatography was also performed on his seminal fluid. The patient showed positive intracutaneous skin tests to his unfractionated seminal plasma and a Sephadex G100 fraction designated No. 3. This fraction was also passively transferable to a nonallergic volunteer and it stimulated histamine release from the patient's leukocytes. The dose-response effects of this fraction compared with unfractionated seminal plasma in these assays showed greater bioactivity. After informed consent was obtained, the patient was immunized to fraction 3 in a classic desensitization protocol. Two weeks after the final dose of immunotherapy, intercourse was performed without condoms in a medical facility and under the supervision of a physician. No adverse symptoms were experienced by the patient on this occasion. Regular and frequent sexual activity is required to maintain her tolerant state.

Immediate anaphylactic reactions after intradiscal chymopapain (CP) injection may occur in 1% of patients undergoing chemonucleolysis (CN). Skin prick testing to CP (10 mg/ml), a prescreening history, and CP serum-specific IgE determinations by the RAST method were performed in order to identify patients presensitized to CP before CN. Follow-up repeat CP skin testing and serum-specific IgE were done 2 to 6 weeks after CN to detect CP IgE-mediated sensitization resulting from the injection. Three of 84 patients who exhibited positive skin tests to CP before CN did not receive CP injections. Only one of the three patients (33%) was detected with elevated CP serum-specific IgE before CN. No immediate severe anaphylactic reactions caused by CP injection were encountered in the remaining 81 patients with negative CP skin tests and RASTs before CN. Eight (10%) nonlife-threatening immediate and late reactions were associated with conversion from negative skin tests and RASTs before CN to positive skin tests or RASTs after CN. Overall, 19 of 52 (37%) patients who returned for follow-up testing developed cutaneous sensitization to CP after CN. Despite the fact that RAST values after CN in these patients were significantly higher (p less than 0.002) than those with negative skin tests after CN, the sensitivity of the RAST was only 72% for identifying patients who developed positive CP skin tests after CN. This study demonstrated that CP skin testing is essential for prescreening patients because it was more sensitive than RAST for identification of CP sensitivity both before and after CN. Late allergic reactions and cutaneous sensitization to CP were common sequelae of CN.

With chymopapain at a concentration of 10 mg/ml, the authors skin tested 540 chemonucleolysis candidates; six were positive, and 534 were negative. None of the positive patients received therapeutic injections of chymopapain. There were no instances of unequivocal anaphylaxis to chymopapain in the patients with negative skin tests treated with chymopapain. When this 0% incidence of systemic reactions in skin test negative patients is compared with the historical rate of 1%, this difference is statistically significant (p less than 0.05). Restriction of chymopapain treatment to patients with negative prick tests can reduce the incidence of systemic reactions.

This is a case report of a patient who developed IgE-mediated sensitization and subsequently ocular angioedema and conjunctivitis from papain contained in a commercial contact lens cleansing solution. Serum-specific IgE and positive cutaneous prick tests to papain and chymopapain were detected. When the lens solution containing papain was stopped, there was resolution of her allergic symptoms. Recognition of this route of papain-induced sensitization may be important in those patients undergoing chemonucleolysis with chymopapain who may be at greater risk to develop a systemic allergic reaction after injection of this enzyme.

A 29-year-old male welder reported systemic reactions after exposure to chromium. Inhalation challenge testing to 29 micrograms/m3 of sodium chromate aerosol resulted in late appearing systemic urticaria, angioedema, and severe bronchospasm that occurred at the same time as a threefold rise in plasma histamine. A direct leukocyte inhibitory factor test to 5.5 X 10(-6)mol/L Na2CrO4 was positive. Although the mechanism of this reaction is unknown, the positive leukocyte inhibitory factor and the general acceptance of hexavalent chromium as a contact skin sensitizer suggest that cell-mediated mechanisms could be involved.