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Abstract

Vulvodynia is a poorly understood, distressing and debilitating disorder. The management of this disorder remains insufficient and the lack of consistent terminology is confusing. The management of classic dysesthetic vulvodynia is fairly straightforward, using drugs effective against chronic neuropathic pain. However, vulvar vestibulitis syndrome remains a therapeutic challenge. A pragmatic approach is recommended for the management of patients with vulvar vestibulitis syndrome. In refractory cases, vestibulectomy has a high success rate, although the evidence is based mainly on small, descriptive studies. Comparative studies of conservative versus surgical management of vulvar vestibulitis syndrome are needed.

Keywords

vestibulitis vestibulitis syndrome vulvar vulvar pain vulvodynia

Recently, there has been an increasing interest in vulvar pain syndrome, or vulvodynia. For instance, the NIH has organized three workshops on vulvodynia since 1997; the last was in April 2003 [1]. Recommendations and research priorities have been outlined in these workshops. Funding for vulvodynia research has also increased. Vulva clinics have been established in many teaching hospitals. Vulvodynia has also become a popular topic in the media and many vulvar pain associations or foundations have emerged. Such organizations have become an important source of information for healthcare professionals and patients alike. Vulvodynia is an emerging chronic pain disorder affecting the quality of life (QoL) of many women. Clearly only the tip of the iceberg has been identified.

Definition

Vulvodynia is a chronic idiopathic vulvar pain syndrome [2]. Patients with vulvodynia suffer from either vulvar hypersensitivity to touch (allodynia) causing dyspareunia, or constant, poorly localized vulvar pain.

History

The history of vulvodynia and vulvar vestibulitis syndrome (VVS) has recently been reviewed [2 –4]. Excessive sensitivity or hyperesthesia of the vulva was first described in 1889 by Skene, and again by Thomas and Munde in 1891. In 1928, Kelly described “exquisitely sensitive deep-red spots in the mucosa of the hymenal ring as a source of dyspareunia.” The International Society for the Study of Vulvar Disease (ISSVD) task force defined vulvodynia as ‘a chronic burning discomfort in the vulva with multiple causes’ in 1980. In 1987, three criteria for the diagnosis of VVS were proposed, including the presence of superficial or entry dyspareunia, the presence of focal or diffuse vestibular erythema, and a positive swab test, where light pressure with a cotton-tipped swab induces a severe pain sensation.

The terminology for vulvodynia used in the literature has been confusing. The term vulvodynia was introduced by Tovell and Young in 1978 [5] and McKay in 1983 [6]. Other terms such as nonpathogenic vulvovaginitis, psychosomatic vulvovaginitis, burning vulva syndrome and vaginismus have also been used. The term VVS was introduced by Friedrich in 1987 [7]. VVS has also been known by other names, such as vestibular adenitis, focal vulvitis or vestibulodynia [8,9].

Constant vulvar pain or dysesthetic vulvodynia has also been called by other names, such as essential vulvodynia, referred nerve root pain or pudendal neuralgia, suggesting that it is a neuropathic pain syndrome [4]. It has many features that are characteristic of other chronic neuropathic pain conditions.

Terminology & classification of vulvar pain

In spite of the widespread use of the terms vestibulitis and dysesthetic vulvodynia, the lack of accuracy of this terminology has caused confusion [10]. In 1999, the ISSVD changed the terminology and classification by replacing the term vulvodynia with dysesthesia. Since not all ISSVD members were happy with this change, the ISSVD came up with another classification, by dividing the subsets of vulvar pain by stimulus. The most recent ISSVD terminology and classification of vulvar pain was developed in 2003 [10]. In this classification, the term vulvodynia is again used. Vulvodynia is defined as vulvar discomfort, most often described as burning pain, occurring in the absence of relevant physical findings or a specific clinically identifiable neurological disorder. Generalized vulvodynia specifies involvement of the whole vulva and localized vulvodynia specifies involvement of a portion of the vulva such as the vestibule. Unprovoked means that the discomfort occurs spontaneously and provoked means that the discomforted is triggered by physical contact. Such contact may be sexual, nonsexual or both. Vestibulitis has been eliminated from the most recent ISSVD terminology, as the presence of inflammation has not always been documented. Therefore, the term vestibulitis has now been replaced by the term ‘provoked vulvodynia’ (Box 1). It is hoped that the new terminology and classification will be acceptable and usable in the future by all physicians involved in the management of patients with vulvar pain. Its use in research may augment the understanding of vulvar pain. In this article, VVS is referred to as provoked vulvodynia and dysesthetic vulvodynia is referred to as unprovoked vulvodynia.

Box 1.

ISSVD terminology and classification of vulvar pain

Generalized

Provoked (sexual, nonsexual or both)

Unprovoked

Mixed (provoked or unprovoked)

Localized

Provoked (sexual, nonsexual or both)

Unprovoked

Mixed (provoked or unprovoked)

Vulvar pain related to a specific disorder

Infectious (e.g., candidiasis, herpes)

Inflammatory (e.g., lichen planus)

Neoplastic (e.g squamous cell carcinoma)

Neurological (e.g. herpes neuralgia, spinal nerve compression)

Vulvodynia is defined as vulvar discomfort, described as burning pain, occurring in the absence of relevant physical findings or specific neurologic disorder ISSVD: International Society for the Study of Vulvar Disease.

Prevalence

The epidemiology of vulvodynia has not been well studied. Similarly, systematic prevalence or incidence studies in different populations do not exist. Limited prevalence studies suggest that up to 15% of women have suffered from vulvodynia at some point in their lives [11]. A recent survey in a community setting in the UK showed a prevalence of 2.8–9.3% [8]. In another recent prevalence survey from the USA, 16% of women had experienced chronic vulvar burning that had lasted 3 months or longer [1]. Approximately 40% of women surveyed had chosen not to seek treatment, even though the symptoms limited sexual activity and QoL. More than 60% of respondents who sought treatment had seen three or more different physicians for the problem. Vulvodynia is responsible for approximately 4% of a total of 36 million physician visits for chronic pain by women in the USA. The age range of vulvodynia patients is highly variable, ranging from adolescents to octagenarians [12]. In general, patients with provoked vulvodynia are younger than those with unprovoked vulvodynia. Descriptive studies suggest that provoked vulvodynia is as common among Caucasian as among African–American women, and even more common among Hispanic women [13,14]. Less than 10% of women with vulvar pain disorders report a history of sexual abuse [12].

Symptoms & clinical findings

Patients describe vulvar pain as burning, stinging, rawness or stabbing, which is difficult to localize [15,16]. Vulvar burning and pain precludes a scratch response. Symptoms may have lasted months or several years. Patients with provoked vulvodynia typically complain of entry dyspareunia, not deep dyspareunia. Women with provoked vulvodynia do not have chronic constant pain that would limit their daily activities. Women with primary provoked vulvodynia have never been able to tolerate introital touch without pain [17]. Women with secondary provoked vulvodynia have had normal sexual activity without pain until vulvodynia developed [17]. Patients with unprovoked vulvodynia complain of constant pain. Typical symptoms include burning, sharp pain, shooting pain and constant aching, which usually gets worse towards the evening.

Meticulous vulvar examination is required. The simple definitive test for provoked vulvodynia requires only a cotton-tipped swab (cotton-swab test). Vestibular-point tenderness at the crypt next to the hymenal ring can be demonstrated in the posterior vestibulum, anterior vestibulum, or both (Figures 1 & 2). Sensitivity and tenderness on touching may be intolerable, making gynecological examination difficult or impossible. Hyperesthesia or pain perceived on light touch is striking and totally out of proportion. This is known as allodynia, meaning that the sensation perceived (pain) differs from that applied (touch). Small, reddened areas as markers of inflammation may or may not be present at the sites of maximum point tenderness. However, reddened vestibular areas are also observed in asymptomatic women undergoing vulvar examination. Therefore, erythema is not a necessary feature of vulvar vestbulitis [18]. On speculum examination, vaginal mucosa appears normal. Wet-mount examination often shows normal Lactobacilli predominating, normal estrogen effect and few white cells, excluding concomitant vaginitis.

Figure 1.

Severe vulvar vestibulitis (provoked vulvodynia).

Figure 2.

Simple swab test used to demonstrate vestibular point tenderness during gynecological examination.

Patients with vulvodynia may suffer from overlapping pain syndromes, such as lower back pain, overactive bladder (OAB), interstitial cystitis, irritable bowel syndrome (IBS) or fibromyalgia [12,19]. Many patients also suffer from depression, which may be secondary to the chronic pain condition.

Pelvic floor muscle (PFM) instability is another important finding among patients with provoked vulvodynia [20 –22]. Women with provoked vulvodynia have elevated rest tension and contractile weakness of PFMs, known as vaginismus. Vaginismus is an involuntary spasm of the muscles surrounding the vagina. This spasm occurs specifically at attempted vaginal entry. It makes penetration difficult and painful, or even impossible. The longer provoked vulvodynia has persisted, the more severe the vaginismus may be.

Diagnosis of vulvodynia

The diagnosis of provoked vulvodynia is clinical and based on history (introital dyspareunia), clinical findings on examination using Friedrich's criteria (point tenderness, often vestibular erythema) [23] and exclusion of other vulvovaginal infections and inflammatory disorders, such as vulvovaginitis or vulvar dermatoses. Introital dyspareunia can be classified into mild (dyspareunia present most of the time, does not prevent sexual intercourse), moderate (dyspareunia always present, intercourse sometimes possible) or severe (dyspareunia totally prohibits intercourse) [24]. Variable degrees of vaginismus may be present. Patients complaining of vulvar pruritus are not likely to have vulvodynia and usually present with skin changes. Patients with unprovoked vulvodynia usually show normal findings on gynecological examination. Unprovoked vulvodynia is often accompanied by psychological disability, severe preoccupation with the pain and major limitation of daily activities.

Histopathology

Vestibular biopsies from vestibulitis cases show mild-to-severe nonspecific chronic inflammation predominantly involving mucosal lamina propria and periglandular tissue [25,26]. However, not all studies have found differences between vestibulitis cases and controls regarding the degree of inflammation [27,28]. Therefore, routine biopsy is of little value in the diagnosis of provoked vulvodynia, but may be necessary to exclude other vulvar pathologies such as inflammatory dermatoses.

Immunohistochemical studies of the peripheral nerve supply of the vestibular mucosa have shown an increased density of intraepithelial nerve bundles or endings, and epithelial nerve-fiber proliferation or sprouting in papillary dermis [29 –32]. A correlation between the degreee of mucosal inflammation and nerve-fiber proliferation has been demonstrated in small case–control studies [31,32]. The cause of the increased density of nerve fibers in patients with provoked vulvodynia is unknown, but could be attributed to an increased presence of nerve growth factors. Vulvar sensation is thought to be mediated by unmyelinated C fibers and myelinated Aδ fibers. Afferent fibers may be sensitized, or an increased density of nerve fibers may lower mechanical and thermal thresholds, leading to the heightened pain perception observed in patients with provoked vulvodynia. The specific cause of an increased density of sensory nerve fibers in patients with provoked vulvodynia is unknown, but could be attributed to an increased local presence of inflammatory mediators. Clearly, understanding this phenomenon may be critical in better understanding the pathogenensis of provoked vulvodynia.

Etiopathogenesis

The etiology of vulvodynia is unknown. This largely reflects the lack of systematic, high-quality basic science and clinical studies of etiology. Most studies of the risk factors or risk markers of vulvodynia have been relatively small, descriptive, case–control studies, and therefore subject to significant selection bias, ascertainment bias and confounding. The level of evidence based on such studies is low, generally level III (comparative studies, correlation studies, case–control studies) or level IV (expert opinion only).

The use of oral contraceptives from an early age and for a period of several years seems to increase the risk for vulvodynia [33]. However, even though this link seems to be relatively strong, it has not been well explained. The higher vestibular sensitivity to mechanical stimulation observed in women using oral contraceptives indicates that these drugs may be one causative factor in vulvar pain. Significantly lower mechanical pain thresholds were observed in the posterior vestibule in the group using oral contraceptives compared with controls [34]. Thus, oral contraceptives may induce increased sensitivity in the vestibular mucosa, which may contribute to the development of provoked vulvodynia. The lower pain threshold may be explained by changes in the vestibular mucosa. Early or prolonged exposure to sex steroid hormones during oral contraceptive use may induce morphological changes and atrophy in the vestibular mucosa, which may influence the mechanical properties and, thus, transduction of mechanical stimuli to the nerve receptors. For instance, pain-conducting nerve endings may be more superficially located if the epithelium has become thinner, thus increasing pain perception.

The role of allergic reactions in the etiology of vulvodynia is not understood. A subset of women with provoked vulvodynia may be sensitized to seminal fluid and this may sometimes be associated with the persistence of symptoms [35].

Literature reviews do not support the etiological role of specific viral or bacterial infections, such as human papillomavirus (HPV), herpes simplex virus, cytomegalovirus or Chlamydia trachomatis. At least 12 small studies have examined the prevalence of HPV DNA in the vestibular tissue of provoked vulvodynia patients, with the prevalence ranging from 0–100%, suggesting no role for HPV [36]. Similarly, response to prolonged treatment with antimycotics (azoles) has been unsatisfactory, suggesting that acute, recurrent or persistent yeast infection does not cause vulvodynia [37]. However, in many cases, vulvodynia symptoms first appear after a severe infection, such as yeast infection, urinary tract infection, other bacterial infection, operative intervention or injury, or postoperative infection. This suggests that there may be a pathogen connection and provoked vulvodynia may be an autoimmune disease [38]. The currently fashionable concept of molecular mimicry suggests that pathogens express a stretch of protein that is related in sequence and structure to a particular self-component. This pathogen-encoded epitope can be presented by the major histocompatibility complex (MHC) and activate self-reactive T-cells. Primed T-cells can then attack self-antigens. The alternative concept of bystander activation proposes that pathogens disturb self-tolerance through inflammation associated with infection. Autoimmunity may fall within the broader and more complex area of microorganism-induced immunopathology. However, to prove these issues for a complex and probably multifactorial disease such as provoked vulvodynia is an extremely difficult task. Mediators released by inflammation or injury can activate unmyelinated C fibers. Prolonged firing of these nerves may sensitize the dorsal horn. Such sensitized neurons may then respond abnormally to input from mechanoreceptors activated by light touch, switching a normal tactile signal to a signal perceived as pain. This allodynia is a characteristic phenomenon among women with provoked vulvodynia. It is also possible that prolonged chronic stimulation and allodynia may eventually establish the sympathetically maintained continuous pain of dysesthetic vulvodynia (central sensitization) [39].

Natural history

Vulvodynia is a chronic, idiopathic pain disorder. In general, the longer the history, the less likely it is that spontaneous recovery will take place. In many cases, symptoms have persisted for several years, sometimes for more than 10 years. This has an enormous negative impact on the health-related QoL of the patient. Pragmatic natural history studies of provoked vulvodynia do not exist. Furthermore, it is not known whether provoked vulvodynia and unprovoked vulvodynia constitute a continuum of the same pain syndrome. Clearly, more natural history studies, as well as basic and clinical research, on vulvodynia are needed.

Psychological aspects

The psychological and psychosexual dimensions of vulvar pain are enormous. The lack of clear-cut physical findings on clinical examination often leads physicians to state that there is nothing wrong. It is easy to attribute the symptoms to a psychosomatic disorder. Provoked vulvodynia is poorly recognized by general practitioners and even by gynecologists, which often leads to so-called ‘doctor shopping’ [40]. Vulvodynia patients, like patients with other chronic pain syndromes, are psychologically distressed and depressed [2]. Chronic pain is often a mystery, causes low self-image, anxiety and isolation, difficulty in sleeping, negative thinking and even suicidal thoughts. Sexual relationships suffer due to sexual dysfunction. Only a few small, case-control studies have attempted to examine the psychological characteristics of vulvodynia patients [41]. Specifically, psychological difficulties within a group of patients with vulvodynia revealed significantly higher levels of psychological distress within the domains of somatization, obsessive–compulsive symptoms, depression, anxiety and phobic symptoms, as well as hostility and paranoia, when validated questionnaires were systematically used [42].

Based on such limited studies, there is no convincing evidence that women with vulvodynia differ from control women regarding specific psychosocial characteristics. Although women with provoked vulvodynia often have complaints such as OAB or IBS, this link can also be secondary. Vulvodynia has been linked to childhood violence victimization, based on self-administered surveys [43]. Vulvodynia was strongly associated with abuse as a child, physically or sexually, on more than one occasion. However, more additional population-based studies of clinically confirmed cases of vulvodynia are needed to replicate this association.

Treatment of unprovoked vulvodynia

The treatment of neuropathic pain syndromes, including unprovoked vulvodynia, is relatively straightforward. Drug treatment for painful sensory neuropathy has recently been reviewed [44]. In general, the treatment of painful sensory neuropathy presents an enormous challenge and is often inadequate. A diary of side effects and preserved benefits should be maintained by patients and shared with the physician, so that drug regimens can be adjusted as necessary. Since monotherapy generally results in a less than 100% reduction in pain at best, a multidrug regimen may be needed.

Tricyclic antidepressants (TCAs) block the reuptake of serotonin and noradrenalin and presumably relieve pain by inhibition of the sodium channel. Most patients with continuous pain respond to tricyclic agents and achieve at least a 50% reduction in pain. However, responses to tricyclics can be insufficient, and the benefits can be outweighed by adverse effects. The next drug of choice is an anticonvulsant, gabapentin or, more recently, pregabalin. Gabapentin is structurally related to γ-aminobutyric acid, a neurotransmitter that plays a role in pain transmission and modulation [45]. Gabapentin monotherapy is well tolerated and is also efficacious in the treatment of diabetic peripheral neuropathy. In some vulvodynia cases, a combination of two drugs, such as amitriptyline and gabapentin, may be more effective and cause fewer adverse effects than either drug alone. Pregabalin is a new and promising gabapentinoid drug that also modulates calcium channels, and is increasingly used in patients with neuropathic pain. Selective serotonin-reuptake inhibitors differ from tricyclic antidepressants in that they selectively block serotonin reuptake, but they are not as effective as tricyclic agents or anticonvulsants against neuropathic pain.

Treatment of provoked vulvodynia

Conservative management

Multiple drugs or therapeutic procedures have been used in the conservative management of provoked vulvodynia. The level of evidence is generally low. A limited number of randomized, controlled trials of the treatment of provoked vulvodynia have been reported [46].

Box 2.

Vestibulectomy in the treatment of provoked vulvodynia.

Total number: 50

Mean age (range): 28.1 (18–48) years

Previous history of pregnancy: 10/50 (20%)

History of OC use: 30/43 (70%)

Duration of symptoms: 4.5 years (1–15 years)

Provoked pain score

– VAS preoperative: 9.2

– VAS postoperative: 2.9

Overall response*

– Complete: 36 (72%)

– Partial: 9 (18%)

– No response: 5 (10%)

A case series from the Vulva Clinic, University Hospital, Helsinki, Finland.

Mean follow-up 33 months; complete response defined as absence of provoked pain during sexual intercourse; partial response defined as mild provoked pain during sexual intercourse not preventing vaginal entry.

OC: Oral contraceptive; VAS: Visual analog scale.

Initial evaluation should include reassurance and exclusion of other causes of dyspareunia or vulvar pain. If vaginismus is present, a biofeedback pelvic musculature training program should be recommended. This is often successful, and more than half of women benefit and may be able to resume intercourse after a few months [47]. Specifically, intravaginal electrical stimulation has proven effective for the treatment of chronic pelvic pain and vestibulitis [48]. A simple pragmatic algorithm used in this author's Vulva Clinic (Helsinki, Finland) for the management of patients with provoked vulvodynia is shown in Figure 3. This algorithm has proven useful in clinical practice. Ultimately, refractory cases undergo vestibulectomy. There are still questions regarding the role of oral contraceptives in the etiopathogenesis of provoked vulvodynia. Although there are no convincing data demonstrating that discontinuation of oral contraceptives has a positive impact on the outcome, anecdotal evidence supports this strategy (Figure 3). However, these young women need contraception and some patients still have intercourse. Other conservative treatment modalities offered to patients before counseling for vestibulectomy include topical lidocaine gel [49], local injections of corticosteroid with lidocaine [50], prolonged used of antifungals (Figure 3) or local injections of botulinum toxin [51,52].

Figure 3.

An algorithm for the management of patients with provoked vulvodynia (vulvar vestibulitis syndrome)

Surgical management

Vestibulectomy in the treatment of refractory, provoked vulvodynia was first described by Woodruff in 1981 [53]. A literature review of outcomes of surgical treatment for provoked vulvodynia showed a significant decrease in symptoms (complete response, partial response or both) in 89% of a total of 646 cases [54]. The author has systematically used vestibulectomy in refractory, provoked vulvodynia cases using the original technique [55]. Briefly, a horse-shoe shaped area of the vestibulum and inner labial fold is excised as one block, followed by dissection of the corresponding posterior vaginal wall proximally to a distance of 4–5 cm. The vaginal mucosa is then easily advanced, replacing the excised vestibular area and approximated and sutured to the perineum using interrupted sutures. Overall, 50 patients have undertaken this procedure during 1995–2004. These patients represent approximately 4% of all new cases referred to the Vulva Clinic during this time period. As shown in Box 2, 90% of the patients had a satisfactory outcome. All except one of the patients said that they would choose the operation again. Thus, a high rate of satisfaction in the most refractory cases can be achieved with proper surgical technique. Compared with other treatment modalities, available surgery clearly provides the best results. However, surgery has so far been considered the last resort for patients with severe, provoked vulvodynia who fail to respond to conservative management.

Comparative studies of surgical versus nonsurgical management

One randomized comparison of cognitive–behavioral therapy, electromyographic biofeedback therapy and vestibulectomy among 78 women with VVS showed that vestibulectomy was more effective than the other two techniques [46]. However, all three treatment groups improved significantly between pretreatment and 6-month follow-up, as measured by pain reduction and sexual function.

Future perspective

It is clear that a better understanding of the pathogenesis of vulvodynia is necessary for the development of new treatment modalities. A research agenda for vulvodynia has been proposed by the NIH [1]. Research priorities include:

Refine the definition of vulvodynia

Start large, multicenter, randomized trials of surgical versus conservative treatment for provoked vulvodynia with long-term follow-up

Develop, standardize and validate methods for evaluating pelvic floor dysfunction

Conduct epidemiological studies to identify risk factors or risk markers for vulvodynia

Define the role of specific microbial pathogens as triggers in the etiopathogenesis of vulvodynia

Executive summary

Vulvodynia is a poorly understood, distressing and debilitating disorder.

Management remains insufficient.

The lack of consistent terminology is confusing.

The management of classic unprovoked vulvodynia is fairly straightforward, using drugs effective against chronic neuropathic pain.

Provoked vulvodynia (vulvar vestibulitis syndrome) remains a therapeutic challenge.

In refractory cases, vestibulectomy has a high success rate, although the evidence is based mostly on small, descriptive studies.

Comparative studies of conservative versus surgical management of provoked vulvodynia are needed.

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Vulvodynia: A Therapeutic Challenge

Abstract

Keywords

Definition

History

Terminology & classification of vulvar pain

Prevalence

Symptoms & clinical findings

Diagnosis of vulvodynia

Histopathology

Etiopathogenesis

Natural history

Psychological aspects

Treatment of unprovoked vulvodynia

Treatment of provoked vulvodynia

Conservative management

Surgical management

Comparative studies of surgical versus nonsurgical management

Future perspective

References