[Detection of the interferon deficiency in inflammatory gynecological diseases and its correction with interferon inducers].

Interferons deficiency has a negative influence on the development of infection and inflammation in general. The use in the complex of anti-inflammatory therapy of interferon inducers (Meglumine acridоnacetate, Tilorone), combining antiviral, immunomodulatory, interferon correction effects with etiopathogenic action leads to the correction of the interferon system defects and eliminate etiological infectious agents, that is confirmed by laboratory data and clinical efficacy.

[Human seminal plasma allergy type I]. / Typ-I-Allergie auf Seminalplasma.

Human seminal plasma allergy (HSPA) is a rare allergic reaction to specific protein fractions of seminal plasma, whereof PSA seems to be a relevant allergen. Predominantly Type I-immunoreactions can occur. The main symptoms are localized and generalized urticaria and sometimes anaphylactic symptoms. The diagnosis is based on history, skin tests and on the determination of specific IgE-levels for (un)fractionated seminal plasma. Here we report a patient with recurrent episodes of generalized urticaria after unprotected sexual intercourse and positive prick-test-reaction on seminal plasma.

Topical misoprostol therapy for plasma cell vulvitis: a case series.

OBJECTIVE: To present the first reported case series of plasma cell vulvitis successfully treated with topical misoprostol. MATERIALS AND METHODS: Three women with vulvar pain and lesions secondary to plasma cell vulvitis refractory to conventional therapy were treated with topical misoprostol compounded in white petrolatum. RESULTS: All three patients had resolution of pain and lesions within 6 weeks of starting topical misoprostol. All patients tolerated the 0.01% concentration; however, local side effects were seen with the higher 0.02% concentration. CONCLUSIONS: Plasma cell vulvitis is a rare and painful vulvar disorder that is often refractory to therapy. All three patients in this case series were successfully treated with topical misoprostol. The immunosuppressive effects of misoprostol are hypothesized to be the mechanisms of action of this novel therapy for plasma cell vulvitis.

Immunoglobulin E antibodies to seminal fluid in women with vulvar vestibulitis syndrome: relation to onset and timing of symptoms.

OBJECTIVE: Patients with vulvar vestibulitis syndrome and control subjects were tested for evidence of allergy to seminal fluid to differentiate women with a clinical diagnosis of vulvar vestibulitis syndrome into discrete categories. STUDY DESIGN: Plasma samples from 52 women with vulvar vestibulitis syndrome and 43 control subjects were tested for immunoglobulin E antibodies to seminal fluid, total immunoglobulin E, interleukin-4, and interleukin-12 by enzyme-linked immunosorbent assay. Demographic and medical histories were obtained by questionnaire and interview. RESULTS: Sixteen of the patients (30.8%) with vulvar vestibulitis syndrome and 2 control subjects (4.7%) tested positive for immunoglobulin E antiseminal fluid. Symptoms began after sexual intercourse in 43.8% of the women who tested immunoglobulin E positive and 11.1% of the women who tested immunoglobulin E negative (P=.02). Symptom initiation after a yeast infection was reported by 31.3% of the women who tested immunoglobulin E positive and by 2.8% of the women who tested immunoglobulin E negative (P=.008). Other symptom-initiating events were reported by 47.2% of the women who tested immunoglobulin E negative and by none of the women who tested immunoglobulin E positive (P=.0008). Fifty percent of the women who tested immunoglobulin E positive, as opposed to 22.2% of the women who tested immunoglobulin E negative, reported pain only after intercourse (P=.05). Pain at other times occurred in 50% of the women who tested immunoglobulin E positive and in 72.2% of the women who tested immunoglobulin E negative (P=.001). There was no relation between immunoglobulin E antiseminal fluid and total immunoglobulin E, interleukin-4,or interleukin-12. CONCLUSION: A subset of women with vulvar vestibulitis syndrome are sensitized to seminal fluid, and an allergic reaction to seminal fluid may be associated with the initiation and persistence of their symptoms.

Defective regulation of the proinflammatory immune response in women with vulvar vestibulitis syndrome.

OBJECTIVE: The cause of vulvar vestibulitis syndrome is unknown. To determine a possible role for defective immune regulation in this chronic condition, proinflammatory and anti-inflammatory immune responses to the 70-kd heat shock protein and to lipopolysaccharide were compared in women with and without vulvar vestibulitis syndrome. STUDY DESIGN: Whole blood cultures from 62 women with vulvar vestibulitis syndrome and 48 control subjects were incubated in the presence or absence of 5 microg/mL human recombinant 70-kd heat shock protein or 0.1 ng/mL lipopolysaccharide for 18 hours. The culture supernatants were then assayed for interleukin-1 beta and interleukin-1 receptor antagonist by enzyme-linked immunosorbent assay. RESULTS: Median levels of interleukin-1 beta were higher in response to heat shock protein in cultures from patients with vulvar vestibulitis syndrome (median, 1.07 ng/mL) as opposed to control subjects (median, 0.40 ng/mL; P =.006). Conversely, levels of interleukin-1 receptor antagonist were higher in response to heat shock protein in control subjects (median, 39.21 ng/mL) than in patients (median, 29.25 ng/mL; P =.009). In response to lipopolysaccharide, median levels of interleukin-1 beta were similar in patients (1.00 ng/mL) and control subjects (1.15 ng/mL); median interleukin-1 receptor antagonist concentrations were higher in control subjects (70.0 ng/mL) than in patients (44.3 ng/mL; P <.0001). The ratio of interleukin-1 receptor antagonist to interleukin-1 beta was higher in control subjects than in women with vulvar vestibulitis syndrome in response to both heat shock protein (P =.0002) and lipopolysaccharide (P =.01). In uninduced cultures, interleukin-1 receptor antagonist levels were also higher in control subjects (median, 1.60 ng/mL) than in patients with vulvar vestibulitis syndrome (median, 0.62 ng/mL; P <.0001). CONCLUSION: A relative inability to down-regulate proinflammatory interleukin-1 beta activity by interleukin-1 receptor antagonist may contribute to the pathophysiologic features of vulvar vestibulitis syndrome.

The expression of cyclooxygenase 2 and inducible nitric oxide synthase indicates no active inflammation in vulvar vestibulitis.

BACKGROUND: Although women with vulvar vestibulitis syndrome have principal symptoms of inflammation such as local erythema and pain in the mucosa around the vaginal introitus, it is not clear if vestibulitis is an inflammatory condition. Cyclooxygenase 2 and inducible nitric oxide synthase are known to be upregulated during inflammation. The aim of the present study was to analyze the expression of these enzymes in the vestibular mucosa in order to evaluate the inflammatory activity in the tissue. METHODS: Ten women fulfilling Friedrich's criteria of vulvar vestibulitis syndrome and ten control subjects were included in the study. Punch biopsies were obtained from the vestibular mucosa for analysis of cyclooxygenas 2 and inducible nitric oxide synthase, using indirect immunohistochemistry and Western dot-blot analyses. RESULTS: Both methods used showed low expression of cyclooxygenas 2 and inducible nitric oxide synthase in the vestibular mucosa of all women. There was no difference observed between the groups. CONCLUSIONS: There is a low expression of the inflammatory markers cyclooxygenas 2 and inducible nitric oxide synthase in the vestibular mucosa of women with vulvar vestibulitis syndrome as well as in healthy control subjects. The results indicate no active inflammation present and imply that topical corticosteroids in the treatment of vulvar vestibulitis are unfounded.

Cromolyn cream for recalcitrant idiopathic vulvar vestibulitis: results of a placebo controlled study.

OBJECTIVE: Patients with chronic idiopathic vulvar vestibulitis have increased mast cells when biopsied, and cromolyn has been suggested as a treatment. The purpose of this study was to assess the efficacy of 4% cromolyn cream in women with vulvar vestibulitis. METHODS: A prospective, double blind, randomised, placebo controlled study was initiated at two centres. Patients with vulvar vestibulitis were assigned to apply cromolyn or placebo cream to the vestibule. Symptoms (burning, irritation) and signs (erythema, extent of erythema, tenderness) were recorded on a 0-3 scale. In the sexually active patient subgroup, dyspareunia was also evaluated. RESULTS: 13 of the 26 evaluable patients received cromolyn. Patients in the cromolyn arm were more likely to have failed therapy with amitriptyline (p = 0.05), but the two groups were otherwise similar upon study entry. Overall, scores decreased from a median of 9 to 5 (p = 0.001) during the study, but the level of improvement was similar between both groups. Improvement was unrelated to duration of symptoms, fluconazole use, or sexual activity. Five patients (38%) taking cromolyn and six (46%) taking placebo felt they had a 50% or greater reduction in symptoms. In the 21 sexually active patients, the total score decreased from a mean of 12 to 8 (p = 0.005), but there was no statistically significant difference between study arms. CONCLUSIONS: Cromolyn cream did not confer a significant benefit in patients with vulvar vestibulitis. The large placebo response suggests the need for large well controlled studies of other treatment modalities.

Interleukin 1 receptor antagonist gene polymorphism in women with vulvar vestibulitis.

OBJECTIVE: Vulvar vestibulitis is a chronic inflammatory syndrome of unknown cause and pathogenesis. We examined the relation between vulvar vestibulitis and polymorphisms in the gene coding for the interleukin 1 receptor antagonist, a naturally occurring down-regulator of proinflammatory immune responses. STUDY DESIGN: Cells from the lower genital tract of 68 women with vulvar vestibulitis, 343 women with no history of vulvodynia, and 40 women with human papillomavirus cervical infection were tested by polymerase chain reaction for the different alleles of the gene encoding for interleukin 1 receptor antagonist. The presence of human papillomavirus in the specimens was determined by polymerase chain reaction with the use of degenerate consensus primers to the conserved L1 gene. RESULTS: Allele 2 of the gene encoding the interleukin 1 receptor antagonist was present in homozygous form in 52.9% of women with vulvar vestibulitis. In marked contrast only 8. 5% of the control women and 2.5% of women with human papillomavirus were homozygous for this allele (P

Vulvitis circumscripta plasmacellularis (Zoon's vulvitis) associated with autoimmune polyglandular endocrine failure.

Vulvitis circumscripta plasmacellularis (Zoon's vulvitis) is a distinct clinicopathological entity which presents as a shiny, atrophic, erythematous plaque of the vulva. It is an idiopathic condition with characteristic clinical and histological findings that generally occur in isolation of other medical disorders. We report a 36-year-old woman with vulvitis circumscripta plasmacellularis associated with polyglandular endocrine failure and circulating autoimmune antibodies. The association between Zoon's vulvitis and these autoimmune conditions raises the possibility that Zoon's vulvitis may be an autoimmune disorder.

Natural killer cell function in women with vestibulitis.

OBJECTIVE: To assess natural killer (NK) cell activity in patients with vestibulitis. STUDY DESIGN: Twenty-two patients who met the International Society for the Study of Vulvar Disease criteria for vestibulitis and 17 age-, sex- and race-matched controls were recruited. NK cell activity was examined using a standard, four-hour 51Cr-release assay, freshly and after stimulation with interleukin 2 (IL2) or alpha interferon (IFN alpha). RESULTS: The subject samples had significantly decreased fresh NK cell activity (mean lytic units [LU]/10(6) peripheral blood leukocytes [PBLs] of 0.93 vs. 4.19, P < .001). This activity was augmented in response to either IFN or IL2. However, it remained significantly lower than in the control samples (12.07 vs. 20.6 LU/10(6) PBL, P = .007 for IL2 and 5.98 vs. 15.33 LU/10(6) PBL, P < .001 for IFN). This difference was not universal since the major histocompatibility-nonrestricted T killer cell activity of the subject samples was not significantly different from that in the control samples. CONCLUSION: This pilot study suggests that patients with vulvar vestibulitis have markedly decreased NK cell activity. Although this activity is increased in response to IL2 or IFN, it remains significantly impaired in comparison to the control samples.

Humoral and secretory antibodies to Ureaplasma diversum in heifers following subcutaneous vaccination and vaginal infection.

We measured antibody levels in serum and cervicovaginal mucus (CVM) of four heifers vaccinated with two inoculations of killed Ureaplasma diversum strain 2312 in incomplete Freund's adjuvant (IFA) two weeks apart, and six heifers given a placebo. Two weeks later, the vaccinates and four placebo heifers, were challenged by intravaginal inoculation with 6.4 x 10(8) colony-forming units of the homologous U. diversum strain. The remaining two placebo heifers served as unvaccinated, unchallenged controls. Antibody levels in serum and CVM of all heifers were determined by an enzyme-linked immunosorbent assay (ELISA). Vaccination stimulated specific IgG1 and IgG2 responses in serum and CVM but only a slight IgM and no IgA response. In both vaccinate and placebo heifers, subsequent intravaginal challenge resulted in a granular vulvitis (GV) with a predominant IgA response in the CVM. The GV gradually subsided during the 35 day observation period but ureaplasmas were consistently demonstrated by culture. We concluded that subcutaneous vaccination stimulated a specific, albeit nonprotective, IgG response in serum and CVM. In contrast, vaginal infection primarily induced a mucosal IgA response.

Two urogenital sinus syndromes. Interstitial cystitis and focal vulvitis.

Forty-six young women had unusual and presumably noninfectious disorders of unknown etiology involving tissues derived from the embryonic urogenital sinus (urogenital sinus syndromes). Ten women had interstitial cystitis, and 25 had focal vulvitis. Eleven women had both interstitial cystitis and focal vulvitis. The affected groups were similar in demographic and other characteristics. Most were white and in their mid-20s. Both unusual conditions occurred in the same woman more often than could be expected by chance. This observation suggests that some common, perhaps autoimmune mechanism may be involved in the etiology of these syndromes.

Immunoglobulin-producing cells in plasma cell orificial mucositis.

Plasma cell orificial mucositis is a benign idiopathic condition of orificial mucous membranes characterized histologically by a dense band-like plasmacytic infiltrate. We studied 8 cases of this disease by immunohistochemical methods for subsets of immunoglobulin-producing cells. The infiltrating plasma cells were found to produce mostly IgG and IgA with the predominance of kappa chain-producing cells over lambda chain-producing cells. This polyclonal plasma cell infiltrate composed of IgG- and IgA-producing cells is in accordance with the pattern observed in the inflammatory infiltrate around certain epidermal neoplasms accompanied by the plasmacytic infiltrate, such as actinic keratosis, Bowen's disease, squamous cell carcinoma, and syringocystadenoma papilliferum.

Papular (erosive) herpes genitalis. A clinical variant in sarcoid and pregnancy.

A unique papular (erosive) variant of herpes genitalis is described in a patient with sarcoid and in 1 who was pregnant. The occurrence of this unique expression of herpes infection in two conditions associated with immunologic changes seems more than incidental. It is suggested that patients presenting with papular (erosive) herpes genitalis be studied for underlying immune deficiency.