and Filippo Murina2
(1)
Center of Gynecology and Medical Sexology, San Raffaele Resnati Hospital, Milan, Italy
(2)
Lower Genital Tract Disease Unit V. Buzzi Hospital, University of Milan, Milan, Italy
Adolescence is the life period when vulvar pain of various etiologies, and specifically vestibulodynia/vulvodynia, begins to be diagnosed, investigated, and treated (Bachmann et al. 2006; Clare and Yeh 2011; Graziottin and Murina 2011; Reed et al. 2014).
The focus of this chapter will be the analysis of different types of vulvar pain in nulliparous adolescents (please see Chap. 7).
Vulvar pain and its different etiologies will be presented with a pathophysiologic reading, carefully based on adolescents’ wording, listened to and questioned during almost four decades of clinical practice by one of the authors (AG) (“practice-based evidence”) and continuously and dynamically analyzed with the ongoing scientific evidence (“evidence-based medicine”).
Vestibulodynia/clitorodynia/vulvodynia are subsets of the vulvar pain. The International Society for the Study of Vulvar Diseases defines vulvodynia as a chronic pain or discomfort involving the vulva for more than 3 months and for which no obvious etiology can be found (Haefner 2007). Vulvodynia descriptors are summarized in Box 6.1.
If the etiology is evident (e.g., lichen sclerosus can affect adolescence as well), then the woman has chronic vulvar pain secondary to lichen sclerosus, if this is the only finding (Sadownik 2014). Thus, vulvodynia is a diagnosis of exclusion. However, the woman could also have both conditions, lichen sclerosus and vestibulodynia that should be carefully evaluated.
Box 6.1. Vulvodynia Descriptors
Women and adolescents with vestibulodynia/vulvodynia do not usually use the word “pain” to describe their discomfort.
They use words such as itching, burning, stinging, irritation, stabbing, and/or rawness.
The classification of vulvodynia is currently based on a description of the pain:
The adolescent’s symptoms may be:
Generalized to the whole vulva (generalized vulvodynia)
Localized to a specific area such as the clitoris (clitorodynia) or the vestibule of the vagina (vestibulodynia)
The pain may be:
Provoked (caused by direct touch, inserting a tampon, or sexual touch)
Unprovoked (spontaneous, i.e., present without touch)
Mixed (Haefner 2007)
Unfortunately, many healthcare providers (HCPs) consider the “dynia” group the paradigm, the unique essence of vulvar pain, which is not. Therefore, a careful listening to and reporting in the medical record of the precise adolescent’s wording may help to exactly qualify her vulvar complaint.
Of note, many predisposing, precipitating, and perpetuating factors are not usually described in the population study on vulvodynia. They will be discussed here because also a few clinical cases may inspire a more comprehensive reading of the complex pathophysiology of vulvar pain. Predictors and vulnerabilities will be briefly considered as well. Preventive strategies with a few key points on treatment principles will be finally summarized (for the detailed discussion, see Chap. 11) (Graziottin and Murina 2011; Frasson et al. 2009; Graziottin 2014; Graziottin et al. 2015; Graziottin and Gambini 2016).
6.1 Epidemiology
Adolescents are the age cohort more vulnerable to vulvar pain. A recent study on 1786 women, assessed for onset of vulvodynia, suggests that the incidence rate was 4.2 cases per 100 person-years, and rates per 100 person-years were greater in women who were younger (7.6 cases per 100 person-years at age 20, compared with 3.3 cases per 100 person-years at age 60), Hispanic (9.5), and married or living as married (4.9); had reported symptoms of vulvar pain but did not meet vulvodynia criteria on the initial survey (11.5); and had reported past symptoms suggesting a history of vulvodynia (7.5). Increased risk of new onset vulvodynia also included baseline sleep disturbance, chronic pain in general, specific comorbid pain disorders, and specific comorbid psychological disorders (Reed et al. 2014). Previous studies suggest an overall prevalence of vulvodynia in the general US population of 8.3 % (Reed et al. 2012a). Chronic vulvar pain may affect up to 16 % of the population, according to other studies (Sadownik 2014). Overall, a prevalence of 7–10 % is the most consistent across studies in the USA (Iglesias-Rios et al. 2015).
6.2 The Narrative of Vulvar Pain in Childhood and Adolescence
Vulvar pain may stem in childhood vulvar lesions:
Vulvar pain is not described nor usually considered in childhood. Pediatricians/clinicians usually refer to “genital pain” when symptoms are referred to the vulvar area in prepubertal girls (Casey et al. 2013), with few exceptions (Clare and Yeh 2011). No follow-up prospective studies of children genital pain/vulvar pain have been found in the available literature, with an important wording/naming and research omission.
When intentional vestibular/vulvar trauma (i.e., sexual abuse) is considered, retrospective studies show conflicting results. Some research groups failed to show any specific association between sexual and physical abuse in childhood and later onset vulvodynia (Cohen-Sacher et al. 2015), while others did well indicate how childhood may be the high-risk age for later chronic vulvar pain, up to specific vulvodynia/vestibulodynia in abused children (Harlow and Stewart 2005; Khandker et al. 2014). Among women with a history of severe childhood abuse, those with vulvodynia had three times the odds of living in fear of any abuse compared to women without vulvodynia (95 % confidence interval: 1.0, 11.0), after adjustment for childhood poverty (Khandker et al. 2014).
Lifelong vestibular/vulvar pain since childhood is a still underinvestigated issue in a subset of adolescents complaining of vestibular/vulvar pain. When specifically questioned, many of them recall that vestibular burning symptoms, with or without bladder symptoms, were present well before puberty, but were not listened to by their family and/or by their pediatrician. Attention to comorbidities is mandatory (Reed et al. 2012b).
Key Point
Listening to and gently asking about vestibular/vulvar pain in childhood is of the highest clinical attention as central components of pain, characterized by a progressive neuroinflammation, may become prominent over the years and make the clinical pain picture much more difficult to be effectively treated in the consulting adolescent.
The sad fact is that vulvar pain in childhood is almost totally neglected worldwide. The inflammation that stimulates pain keeps therefore on being active in the shadow of physicians’ diagnostic omission. When finally the consulted gynecologist diagnoses vestibular and/or vulvar pain since puberty, quite a long period of childhood chronic vulvar pain may have gone undetected.
In other case, vestibular/vulvar pain may be complained of after the very first(s) intercourses: it is defined as lifelong vestibular/vulvar pain since adolescence. In these cases it can be a new symptom in a girl otherwise healthy from the general, genital, and vulvar point of view until the symptom was first complained of.
Key Point
When conflicting results are reported, the authors of this book focus on the pathophysiology of vulvar pain and vestibulodynia/vulvodynia to give meaning to those results, with the aim of distilling useful infos for the clinicians in their daily practice first and researchers second.
6.3 Vulvar Pain: The New Entry in Adolescents’ Diagnostic Scenario
Why is there such a change in the diagnostic/naming attitude of physicians, who finally call vulvar pain the formerly defined “genital pain,” or “female genital pain”?
Reasons include, but are not limited to:
Habit, as the literature tends to be quite conservative in the diagnostic labeling, unless major discussion arises worldwide.
Different training and diagnostic attitudes between gynecologists, trained to call the vulva with this name, whatever the age of the patient, and pediatricians, trained to generally call the vulva “genital.” However, pediatricians correctly call differently the glans, the penis, and the scrotum of little boys, without encompassing them all in the term “genitals,” as they do for girls (Casey et al. 2013).
The tendency to talk about vulvar pain in adolescents and young women in reproductive age, when genital pain is associated with sexual intercourse or early tampon use (Clare and Yeh 2011).
The sexual reading of the vulva, so that the name is (unconsciously?) considered appropriate for the organ only after puberty.
6.4 Risk Factors for Vulvar Pain in Adolescence
Risk factors can be clustered under three major headings: predisposing, precipitating, and perpetuating factors, for the sake of clarity. The goal is to facilitate a more structured learning, hopefully useful in the clinical practice.
In real life risk factors for vulvar pain in adolescence may partly overlap. This is specifically true for the sexual factor, a major player in the game of predisposing, precipitating, and perpetuating factors.
The skilled physician should try to make the more comprehensive diagnosis with a careful evaluation of the different factors more relevant in the individual case (Box 6.2).
Box 6.2. The Pain Movie
The diagnosis is a photogram in the movie, i.e., in the film of a disorder or a disease. The skilled clinician should look at the photogram of the vestibular/vulvar pain complaint (or any other pain) with an investigative and pathophysiologically oriented mind. He/she should look for the protagonist(s) of the pain movie, for the co-protagonists, and for the passing-by actors reading carefully (within) the plot. From the medical point of view, predisposing, precipitating, and perpetuating factors/actors should be recognized.
The skilled clinician knows that the photogram of the first diagnosis identifies a critical crossroad. According to the adequacy and quality of the diagnosis and consequent multimodal treatment decisions, the pain movie can continue with different narrative plots, until a:
Dramatic end: a neuropathic persistent devastating pain when it is neglected, banalized, undiagnosed, and untreated
Disappointing end, when the diagnosis is inadequate and/or incomplete and when treatment is minimalistic, partial, short-living, or inappropriately surgically aggressive
Very rewarding happy end, when predisposing, precipitating, and perpetuating factors are diagnosed and treated and when the pharmacologic treatment is successful in addressing the central neuroinflammatory component of the pain process
6.5 Predisposing Factors
6.5.1 Traumas
Unintentional sportive and other types of accidental vulvar traumas may cause vulvar pain in adolescents, similar to what happens during childhood (Smith et al. 2013).
Genitofemoral neuralgia is often the consequence of such traumas, in adolescent and, as well, in adult women (Verstraelen et al. 2015). Pain may be perceived and complained of immediately after the trauma (acute vulvar pain) and then resolved. It may reappear and/or worsen months and years after the primary insult.
Vulvar pain may also be the result of a pudendal neuralgia of posttraumatic origin, for example, after a traumatic fall over the coccygis years before the clinical complaint of vulvar pain (Graziottin et al. 2015).
Intentional traumas, such as sexual abuse, are discussed below under the heading of precipitating sexual factors (please see also Chap. 4).
Female genital mutilation/cutting (FMG/C) is a traumatic and potentially devastating cause of vulvar pain when performed during the childhood and, probably even more, after puberty. The many issues involved are discussed in detail in the pertinent chapter (please see the Chap. 5).
Key Point
Vulvar and pelvic traumas should be actively questioned in every adolescent complaining of vulvar pain. The girl should be encouraged to recall childhood traumas, if present, and to ask the mother about this event even at a very small age, particularly when a coccygeal trauma and a pudendal neuralgia appear as potential contributors.
6.5.2 Herpes Virus 1 and 2 (HSV1, HSV2)
Herpes virus type 2 vulvitis is more prevalent than thought. A recent study shows that in Germany HSV-2 prevalence increases from ~3 % in children aged 10–15 years to 7 % among 16–18-year-olds and to 14 % among adults. It causes acute vulvar pain, itching, and burning; in a subset of cases, it may cause intermittent recurrent infections (see the excellent review of Sauerbrei 2016).
HSV-1 and HSV-2 may cause peripheral neuropathy. In rare cases this may evolve to chronic neuropathic vulvar pain.
6.5.3 Papillomavirus
The role of papillomavirus-induced vulvar lesions as potential triggers of vulvar pain is still under debate (Graziottin and Serafini 2012).
The most credited reading is that not the HPV infections per se but the outcome of treatments (laser, thermocoagulation, thermic) may be responsible for the subset of vulvar pain complained of after an HPV infection (Graziottin and Serafini 2012).
6.5.4 Vulvar Lichen Sclerosus
Vulvar lichen sclerosus (VLS) is an autoimmune disease of genital/vulvar and extragenital skin (Fistarol and Itin 2013). It causes chronic inflammation of the vulvar tissue, with progressive full-thickness tissue destruction of the vulvar cytoarchitecture and function. Labia involution, thinning, and clitoral conglutination of the hood may result. It may affect children (please see the clinical case described in Chap. 4) and adolescents, with prevalence increasing with age. The main symptom is vulvar itching, more disturbing and intense at night. Itching is a subtype of pain. When people feel itching, MRI indicates that brain pain areas are activated. When people scratch the itching area, brain pain areas are silenced and pleasure/reward mediating areas are activated. Other symptoms include pain, dysuria, and restriction of micturition.
In the long term, if left untreated, VLS causes the full-thickness tissue involution which progresses to involve as well the corpora cavernosa. A progressive reduction of the sexual response may then be complained of, in parallel to the worsening itching, unless appropriate treatment is adequately prescribed in the long term. Treatment includes topical cortisone, topical testosterone (of vegetal origin or propionate), and vitamin E cream. They are usually adequate to control both symptoms and the progression of the disease. VLS deserves periodic clinical monitoring, as 5 % may evolve to vulvar cancer (Fistarol and Itin 2013). The probability is higher in cases with early onset.
When VLS causes progressive stenosis of the vestibular area and of the vaginal entrance, it may cause severe introital dyspareunia and progressive sexual dysfunction in women (Fistarol and Itin 2013): this is usually a late complication, but it may be an unexpected contributing factor to introital pain also in young women. Treatment of lichen sclerosus in the adolescence requires a very careful and competent approach (Gurumurthy et al. 2012; Simonetta et al. 2015).
6.5.5 Sexual Factor
The sexual factor is a major protagonist in the narrative of vestibular pain in adolescents. It may behave as:
Predisposing factor, when it causes the first inflammatory trauma of the vestibular mucosa, which was normal and healthy until that very moment.
Precipitating factor, when it exacerbates the role of other predisposing factors such as a hyperactive pelvic floor and/or a recurrent Candida vaginitis or of vaginal dryness associated with hypothalamic amenorrhea or hormonal contraceptive use.
Perpetuating factor, when the adolescent continues to accept the intercourse, with the consequent repeated mechanical trauma of the introital mucosa, in spite of a worsening pain, for fear of being abandoned, or in the vain hope that insisting on having intercourse will “cure” the problem, or because she is forced to accept intercourse by an abusive partner. A dramatic iatrogenic component is in play when some physicians recommend the use of an anesthetic cream “to allow the intercourse with less pain.” In the short term, this antitherapeutic suggestion may seem to reduce pain during intercourse, but it will perpetuate a worsening trauma of the vestibular mucosa. Which physician would recommend the use of an anesthetic to allow the walking on a broken leg? Why should he/she recommend the anesthetic to allow the partner to “use” a wounded, inflamed vestibule and vagina?
The focused listening to adolescents reporting their experiences “in their own words” across many decades of clinical practice leads one of the authors (AG) to identify different pain experiences contributing to different types of vulvar and vestibular pain and to understand why the sexual factor plays a major role in the etiology of vestibular and vulvar pain and associated comorbidities.
Different types of vestibular/vulvar pain will be described in a polarized structured approach for the sake of clarity. In real life intermediate pathophysiologic mechanisms can be in play. This description is aimed at giving clinical meaning to adolescents’ wording and to ease the diagnostic and therapeutic work of clinicians who are committed to help their young patients in their daily work.
The scenario of vulvar pain triggered by sexual intercourse presents with different leading features:
- 1.
Acute transient nociceptive vestibular pain and acute introital dyspareunia
- 2.
Chronic/intermittent vestibular pain and recurrent introital dyspareunia
- 3.
Lifelong (primary) neuropathic vestibular pain and lifelong introital dyspareunia
- 4.
Acquired (secondary) vestibular pain and acquired introital dyspareunia, either acute/nociceptive or, later, chronic and then neuropathic
The descriptions focus first on desired, accepted first experiences, to analyze the biological mechanisms that are in play in the perception of sexually triggered vestibular pain.
Unwanted sex, sexual harassment, and sexual assault may further complicate the vulvar pain scenario according to the adolescent’s (or child’s!) age, the identity of the perpetrator (relative, acquaintance, or unknown), the severity of the physical trauma and other associated lesions, emotional and psychosexual impact of the sexual trauma, frequency of sexual abuse, the emotional context, quality of family support (or neglect), and quality of medical and psychological support.
Key Point
The precise gentle questioning about the presence of vestibular/vulvar (and/or bladder) pain during childhood is a vital part of the medical history. Causes of childhood vulvar pain should be quoted with the adolescent’s words. Specific traumatic events, including sexual abuse but also painful diagnostic genital/vulvar maneuvers during childhood (such as suturing of labia’s unintentional trauma without analgesia/anesthesia, repeated urethral catheterization for whatever reason, and so on), should be investigated and recorded. In the author’s (AG) experience, in 5.3 % of later vulvar pain, the only recalled childhood trauma was linked to medical invasive exams, such as urethroscopy, tampon swab, vaginal swab, “urethral dilatation,” suturing of unintentional traumas without analgesia, and so on.
The four different types of vulvar pain triggered by sexual intercourse will be briefly discussed, trying to identify critical passages and pathophysiologically relevant events contributing to the shift from acute to chronic to neuropathic pain.
6.5.5.1 Acute Transient Nociceptive Vestibular Pain and Acute Introital Dyspareunia
Almost every adolescent girl can experience short-living, transient acute vestibular pain and introital dyspareunia of variable intensity, from very mild/negligible to severe, at first desired sexual intercourse or a few more, when the hymen is broken during the first penetration(s).
This pain is triggered by hymenal sexual abrasions/lacerations/lesions; it has a “microtraumatic” etiology; it is “nociceptive,” i.e., it indicates a tissue damage that should be repaired by the physiologic inflammatory process. It indicates therefore the presence of a transient hymenal mucosal damage that normally will be rapidly repaired by an inflammatory process of limited intensity and duration, finalized to restore the normal anatomic and physiologic conditions (“resolving inflammation”) (Fig. 6.1).
Fig. 6.1
Inflammation’s key features are summarized here. The figure highlights the fact that inflammation is a physiologic process necessary to maintain health when it is “resolving,” i.e., when it is finalized to restore the normal cytoarchitecture and function of a tissue, after an infection or a trauma. Typical examples of physiologic, periodic inflammation include ovulation, menstruation, or delivery, just to mention three typical events in women’s health. When inflammation is physiologic, it is also, by definition, of limited duration, sufficient to restore the normal tissue well-being, and of limited intensity. Inflammation becomes progressively pathologic when it is non-resolving and chronic and when it becomes more and more severe and invalidating (Graziottin 2015b)
Vestibular pain can be repeated and more prolonged when a tightened, fibrous, rigid hymen is present. After a few more attempts, if there are no other cofactors, if the desire and arousal of the girl remain intense, and if the sense of intimacy and love is emotionally rewarding, then the hymen is gradually dilated and a normal, painless intercourse can be finally enjoyed.
6.5.5.2 Chronic/Intermittent Vestibular Pain and Recurrent Introital Dyspareunia
Vestibular pain triggered by sexual intercourse persists beyond 36 months when:
The hymen is cribrous, or very thick.
A hyperactive pelvic floor is present.
Fear of pain (up to a frank vaginismus) blocks the genital arousal, leading to vaginal dryness, and further triggers a defensive contraction of the levator ani.
Sexual pain (introital dyspareunia) inhibits sexual desire and central and peripheral arousal (Graziottin 2015a).
Penetration can therefore become extremely painful or impossible. If the partner insists in his attempts, an inflammatory repeated trauma of variable intensity, of the vestibular area, and of the external part of the hymen is in play. Mast cells are a critical factor in the activation and persistence of inflammation progressively moving from the genitals to the brain (Graziottin et al. 2013, 2014; Skaper et al. 2014).
This vestibular/hymenal inflammation can:
Finally resolve (“resolving inflammation,” a physiologic process), when the penetration is accomplished, the girl manages to relax the pelvic floor, and the residual hymenal remnants gradually heal with a nonpainful residual scar
Be maintained and become a “chronic vestibular inflammation” of the vestibular area, with continuous or intermittent sexual pain at intercourse
Vaginismus with myogenic hyperactivity of the levator ani may be so biologically driven to require pharmacologic treatment with botulinum toxin. Otherwise it will perpetuate as persistent predisposing factor to introital trauma and chronic vestibular inflammation. A botulinum toxin treatment (Bertolasi et al. 2009) may be necessary both in primary and secondary vaginismus when the myogenic component is nonresponsive to conventional psycho-behavioral and physiotherapic treatments. Central components of vaginismus should be assessed as well (Frasson et al. 2009).
6.5.5.3 Lifelong (Primary) Neuropathic Vestibular Pain and Lifelong Introital Dyspareunia
When the microtraumatic abrasions of the introital mucosa are repeated, the inflammatory process further changes its characteristics within the vestibular mucosa:
From “resolving,” finalized at restoring the normal cytoarchitecture and integrity of the vestibular mucosa, with a limited duration and intensity, the inflammatory process gradually shifts into a lifelong vulvar vestibulitis since adolescence.
Mast cell involvement (Graziottin 2009; Graziottin et al. 2013, 2014) significantly increases, with increased production and release within the vestibular mucosa of many cytokines, of nerve growth factor (NGF), and of other neurotrophins. Local proliferation of nerve pain fibers is the histologic correlate of the hyperalgesia, i.e., the amplification of the intensity of the stimulus perceived by the woman. Mast cells produce as well tryptase and heparanase, lytic enzymes responsible for the creation of tunnels across the basal membrane.
Pain fibers penetrate along these microscopic tunnels and superficialize across the cells of the vestibular mucosa. This process is responsible for another typical pain feature: pain perception shifts from a tactile stimulus into “burning pain,” “as if I were burned with a hot iron,” as many young women frequently say to the listening physician. This shifting is defined as allodynia and is typically found when the physician gently touches (“tactile stimulus”) at 5 and 7 o’clock of the vestibular introitus, looking at it as a clock face, and the woman perceives a burning pain. The tactile stimulus is then “read” by the brain as a painful one.
Lifelong “provoked vestibulodynia” is the current definition of this specific pain experience that is the leading etiology of lifelong introital dyspareunia, i.e., persistently painful intercourse in adolescents.
The very same type of vestibular burning pain is experienced during and after intercourse.
Pelvic symptoms and comorbidities are increasingly reported, when the vestibular inflammation mechanically induced by the intercourse persists and is reactivated at every penetration. The inflammatory process tends to involve the neighboring organs, the urethra and the bladder first. This involvement is more likely when a hyperactive pelvic floor, either lifelong and/or acquired in response to pain, is in play (Graziottin 2014, 2015a; Graziottin and Gambini 2015; Graziottin et al. 2016).
Recurrent cystitis and provoked vestibulodynia are reported by 60 % of women when accurately investigated (Salonia et al. 2013). Postcoital cystitis, usually complained of 24–72 h after intercourse, and a pain bladder syndrome (Peters et al. 2007) are frequently reported in the natural history of lifelong vulvar vestibulitis/provoked vestibulodynia and introital dyspareunia since adolescence.
Neuroinflammation becomes a prominent feature when the inflammatory process becomes non-resolving, i.e., unable to restore the return to normal anatomic and physiologic conditions, either because the precipitating traumatic factor (intercourse) is repeated or because other contributing factors (see below) remain undiagnosed/unaddressed (Xanthos et al. 2011; Walker et al. 2013; Ru-Rong et al. 2014; Xanthos and Sandkühler 2014).
When the hyperactivated mast cells keep on producing and releasing in the tissue inflammatory molecules such as cytokines, tumor necrosis factor alpha, and others, a progressive neuroinflammation takes place. Neuroinflammation is characterized by infiltration of immune cells, activation of glial cells, and production of inflammatory mediators in the peripheral and central nervous system (Ru-Rong et al. 2014). It has an important role in the induction and maintenance of chronic pain. Inflammatory molecules can either pass across the brain barrier and/or be produced within the brain by the hyperactivated microglia (Xanthos et al. 2011; Walker et al. 2013; Ru-Rong et al. 2014; Xanthos and Sandkühler 2014).
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