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Trigonitis) Can Be Challenging and Frustrating for Both the Triad of findings: 1) Severe Pain with Vestibular Touch Or Patient and Clinician

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Trigonitis) Can Be Challenging and Frustrating for Both the Triad of findings: 1) Severe Pain with Vestibular Touch Or Patient and Clinician 9-2 Painful Conditions of the Urogenital Sinus Nathan Guerette and G.Willy Davila Diagnosis and treatment of lower urogenital pain condi- Friedrich3 characterized vulvar vestibulitis as a persist- tions (vulvar vestibulitis, urethral pain syndrome, and ent syndrome lasting more than 6 months consisting of a trigonitis) can be challenging and frustrating for both the triad of findings: 1) severe pain with vestibular touch or patient and clinician. However, a methodical approach to attempted vaginal penetration, 2) tenderness in response evaluation and management can lead to remarkable to pressure within the vulvar vestibule, and 3) physical improvements. findings of erythema confined to the vestibule of varying degrees. Embryology Clinical Presentation In early female gestation, the cloaca separates into anterior and posterior divisions. The anterior division develops into Typically, patients will present with a history of vaginal the urogenital sinus. This endodermal structure then pain or burning and dyspareunia. Upon further question- morphs into the bladder, urethra, and vaginal bulb. The ing, the pain is localized to the introitus and usually bulb forms a portion of the superior vagina and inferiorly described as a burning or cutting that initiates with entry. fuses with the genital ectoderm. This fusion point forms Often tampon insertion or other activities increasing pres- the vulvar vestibule. sure in the vestibule will elicit similar symptoms. Many The common embryologic origin of the vestibule, patients will present with “recurrent cystitis,” caused by urethra, and bladder has suggested an etiologic association episodic burning with urination. Upon detailed question- among chronic painful conditions involving these tissues. ing, it is determined that the burning is external, typically This may help explain the similarity in physical and histo- after voiding and frequently with negative urine cultures, logic findings, prevalence rates, and treatment strategies and it resolves whether or not antibiotics are taken. for vulvar vestibulitis, trigonitis, urethritis, and interstitial Other vulvar dysesthesias can be difficult to distinguish cystitis.1,2 Interstitial cystitis is considered in a separate from vestibulitis. The key difference is that vulvar vestibu- chapter. litis has provoked symptoms, with pain initiated by direct physical contact. Women with vestibulitis will often have great apprehension about sexual intercourse and largely Vulvar Vestibulitis cease activity secondary to the degree of pain. Distinctions have been made between women with Anatomy and Definition primary vestibulitis, dyspareunia at the initiation of their sexual experience, and secondary vestibulitis (dyspareunia The vulvar vestibule is the most inferior portion of the after a time of asymptomatic intercourse) because patients urogenital sinus. It is a ringed structure delineated superi- with primary vestibulitis do not tend to respond as well to orly by the hymen, inferiorly by the more pigmented skin treatment.4 at the base of the labium minus (Hart’s line), anteriorly by the clitoris, and posteriorly by the fourchette and fossa navicularis. It is composed of thinly keratinized stratified Epidemiology and Demographics squamous epithelium. The urethra, Bartholin’s glands, Skene’s glands, and numerous minor mucous glands drain No large studies have been performed to accurately esti- into the vestibule. mate the prevalence of vestibulitis in the population. In 251 252 Pain and Irritative Syndromes Therapy 1995, Baggish and Miklos5 performed a meta-analysis of 15 natural killer cell activity increases after application of studies with 450 patients in an attempt to more accurately interferon.17 characterize women with vulvar vestibulitis. The typical vulvar vestibulitis patient is white, nulliparous, well- educated, and young. The women have frequently seen Etiology multiple clinicians, and have sought treatment for 2 to 3 years before the diagnosis is made. Many are diagnosed Numerous theories have been investigated to identify the with recurrent urinary tract infections,candidal infections, etiology of vulvar vestibulitis. Chronic bacterial and viral human papillomavirus (HPV), and allergies. An increased infections have been the strongest focus of study. Candida, rate of prior sexual abuse in these patients has been chlamydia, gonorrhea, mycoplasma, contact dermatitis and reported, but is controversial.6,7 other allergic responses, hormonal reaction, and psycho- Psychological testing on women with vulvar vestibulitis somatic causes have also been considered. Despite these has found higher rates of introversion, somatization, and extensive investigations, the etiology remains unclear and interference with sexual function. Overall levels of psycho- may be multifactorial. logical distress, negative feelings toward sex, self-esteem, Human papillomavirus has been the most thoroughly and marital satisfaction are conflicted in the literature with studied virus as an etiology. Numerous studies have tried some studies showing no difference from matched controls to correlate the presence of HPV with vulvar vestibulitis and others finding opposite results. Furthermore, the order symptoms, but the results have been highly variable, of causation remains unclear, with many authors suggest- reporting 0% to 85% rates of identifiable HPV in vestibu- ing a circular relationship of the physical condition and litis patients.18–22 In addition, no difference has been noted psychological changes.8–10 in HPV-positive and -negative women in response to treat- ment.23 Human papillomavirus does not seem to be causative or, if present, affect treatment outcomes. Histopathology During the initiation of urination, urine separates the labia minora and thus wets the entire vestibule, thus, Historic terms for vulvar vestibulitis (vulvar adenitis, ery- contact with urinary irritants, particularly oxalates, has thematous vulvitis, burning vulva syndrome) all implicate been researched as a possible etiology. Oxalates are organic inflammatory changes, but it was not until the late 1970s acids excreted in the urine that can cause pruritus and and 1980s that the histologic changes associated with burning. Many studies have shown higher rates of hyper- vestibulitis were better characterized. oxaluria in women with vestibulitis. These findings, A 1988 study analyzed 41 surgical specimens from however, have been inconsistent.24–26 patients diagnosed with vulvar vestibulitis. Chronic inter- stitial inflammation was seen in all cases and the glands were not involved. The etiology of this inflammation was Evaluation undetermined.7 More recently, controlled studies have produced more mixed results with similar patterns of A careful evaluation is necessary to design an effective inflammation but often no differences from control treatment regimen. We obtain a thorough history, includ- specimens.6,11,12 ing previous treatments and any contributing psychologi- When investigating hypotheses that vascular injury, cal factors, including sexual abuse, when timing is immunologic alterations, or changes in nociception may be appropriate.A broad differential should be used to rule out contributing factors, additional histologic findings have other vulvar or vaginal conditions such as candidal vagini- been noted. Inflammatory cytokines interleukin-1 and tis,lichen planus,or a chronic abscess of Bartholin’s glands. tumor necrosis factor were elevated in vestibulitis speci- Any potential allergens or irritants should be identified. mens compared with perineoplasty specimens from Particular attention should be given to patterns of exacer- asymptomatic women.13 Increased levels of perivascular bation of vestibulitis symptoms in conjunction with immunoglobulin M,complement,and fibrinogen,as well as ingestion of foods with high oxalate concentrations. For heightened angiogenesis have been noted in vestibulitis example, we have found a strong relationship between specimens compared with controls.14 Studies have noted consumption of various types of berries and worsening increased neural hyperplasia in vestibulitis subjects and symptoms. found the degree of vestibular nerve formation When vestibulitis is suspected, a detailed vulvar and significantly correlated with the degree of inflamma- vaginal examination must be performed. Any cutaneous tion.15,16 Whether these changes are causative or secondary or mucosal abnormalities as well as atrophic changes in remains unclear. the vaginal mucosa should be noted. The vestibule must Immune dysfunction has also been postulated as an be inspected for erythema and other signs of chronic underlying factor in vulvar vestibulitis with decreased inflammation. Pain mapping with a cotton-tipped swab natural killer cell activity in the vestibular tissues of should be done, before any vaginal instrumentation, symptomatic women. It has also been observed that to delineate the area of sensitivity (Figure 9-2.1). This Painful Conditions of the Urogenital Sinus 253 Upper genital tract pain, elicited on bimanual examination, may be suggestive of pelvic inflammatory disease, endometriosis, or a pelvic mass. A gentle, methodical approach to the vulvovaginal examination in patients with a history suggestive of urogenital sinus pain is imperative. Treatment Education Women diagnosed with vulvar vestibulitis, particularly at specialty centers, have usually seen multiple clinicians, received numerous courses of medications for infections, and have often been told the problem is psychological. Giving
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